Composite Adverse Pregnancy Outcome Research Articles

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<0.00001) and had a lower gestational weight gain (8.6±5.4 vs. 10.8±6.1 kg, p<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.

Marijuana Use in Pregnancy: Does the High Make You High Risk? [20E

INTRODUCTION: To identify adverse pregnancy outcomes associated with marijuana use during pregnancy. METHODS: We conducted a secondary analysis of the prospective cohort study, “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” (nuMoM2b), which recruited 10,038 nulliparous women with singleton pregnancies from eight U.S. medical centers. Information regarding marijuana use was obtained using direct questionnaires during in-person interview. The composite adverse outcome included stillbirth, hypertensive disorders of pregnancy, preterm birth, and small-for-gestational-age births. Secondary outcomes assessed neonatal morbidity, specifically examining neonatal intensive care unit admission, respiratory distress syndrome, neonatal sepsis, and neonatal death. Other secondary outcomes included mode of delivery and suspected intrauterine fetal growth restriction. RESULTS: Marijuana use during pregnancy was identified in 1.3% of the nulliparous women with singleton pregnancies. Marijuana users during pregnancy were found to have an increased risk of the composite adverse outcome compared to nonusers (27.6% vs 20.4%; P=.049) with an increase small-for-gestational-age births (16.6% vs 9.5%; P=.021). After adjustment for age, BMI, race, and chronic hypertension, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio 1.27; 95% CI 0.84–1.89). CONCLUSION: Maternal marijuana use is potentially associated with an increased risk of composite adverse pregnancy outcome of stillbirth, hypertensive disorders of pregnancy, preterm birth, and small-for-gestational-age births. However, the association was not significant when controlling for possible confounders. Future studies should focus on biologic evidence of marijuana consumption as compared to self-report.

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

TB prevention strategies and unanswered questions for pregnant and postpartum women living with HIV: the need for improved evidence.

Standard care informed by the result of a placental growth factor blood test versus standard care alone in women with reduced fetal movement at or after 36+0 weeks\u2019 gestation: a pilot randomised controlled trial

BackgroundBiomarkers of placental function can potentially aid the diagnosis and prediction of pregnancy complications. This randomised controlled pilot trial assessed whether for women with reduced fetal movement (RFM), intervention directed by the measurement of a placental biomarker in addition to standard care was feasible and improved pregnancy outcome compared with standard care alone.MethodsWomen aged 16–50 years presenting at eight UK maternity units with RFM between 36+0 and 41+0 weeks’ gestation with a viable singleton pregnancy and no indication for immediate delivery were eligible. Participants were randomised 1:1 in an unblinded manner to standard care and a biomarker blood test result revealed and acted on (intervention arm) or standard care where the biomarker result was not available (control arm). The objectives were to determine the feasibility of a main trial by recruiting 175–225 participants over 9 months and to provide proof of concept that informing care by measurement of placental biomarkers may improve outcome. Feasibility was assessed via the number of potentially eligible women, number recruited, reasons for non-recruitment and compliance. Proof of concept outcomes included the rates of the induction of labour and caesarean birth, and a composite adverse pregnancy outcome.ResultsOverall, 2917 women presented with RFM ≥ 36 weeks, 352 were approached to participate and 216 (61%) were randomised (intervention n = 109, control n = 107). The main reason for not approaching women was resource/staff issues (n = 1510). Ninety-seven women declined the trial, mainly due to not liking blood tests (n = 24) or not wanting to be in a trial (n = 21). Compliance with the trial interventions was 100% in both arms. Labour was induced in 97 (45%) participants (intervention n = 49, control n = 48), while 17 (9%) had planned caesarean sections (intervention n = 9, control n = 8). Overall, 9 (8%) babies in the intervention arm had the composite adverse pregnancy outcome versus 4 (4%) in the control arm.ConclusionsA main trial using a placental biomarker in combination with delivery, as indicated by the biomarker, in women with RFM is feasible. The frequency of adverse outcomes in this population is low, hence, a large sample size would be required along with consideration of the most appropriate outcome measures.Trial registrationISRCTN, ISRCTN12067514; registered 8 September 2017.

Vitamin D Concentration during Early Pregnancy and Adverse Outcomes among HIV-Negative Women in Dar-es-Salaam, Tanzania: A Case-Control Study.

We examined the associations of plasma vitamin D concentration and adverse pregnancy outcomes among HIV-negative women in Dar-es-Salaam, Tanzania. We used an unmatched case-control study design, with 25-hydroxyvitamin D [25(OH)D] concentration assessed in the first trimester. Cases were individuals with adverse pregnancy outcomes, including stillbirth, premature birth, or small for gestational age births (SGA). Unconditional logistic regression and weighted logistic regression models were used to describe the associations of 25(OH)D concentration with the composite of adverse pregnancy outcome and individual adverse pregnancy outcomes, respectively. We included 310 cases and 321 controls. In controls, 5(2%) were vitamin D deficient (25(OH)D < 20 ng/mL), and 17(5%) had insufficient 25(OH)D concentration (20.0–29.9 ng/mL). Women with 25(OH)D < 20 ng/mL had 1.82 times the odds of occurrence of the composite adverse pregnancy outcome (OR = 1.82, 95% CI: 0.56–5.93; p = 0.32), however we noted a non-linear association between 25(OH)D concentration and adverse pregnancy outcome (p = 0.02). We found a 3-fold increased odds of stillbirth in women with low 25(OH)D concentration (OR = 3.11, 95% CI: 1.18–8.23, p = 0.02). Vitamin D concentration in early pregnancy may be an important factor in determining the course of pregnancy. Further research is needed to investigate whether the association of maternal 25(OH)D concentration in early pregnancy and stillbirth is causal.

Isoniazid Preventive Therapy in HIV-Infected Pregnant and Postpartum Women

BackgroundThe safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown.MethodsIn this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years.ResultsA total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], −4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, −0.39; 95% CI, −1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, −0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9).ConclusionsThe risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.)

Umbilical arterial Doppler ultrasonography predicts late pregnancy outcomes in patients with lupus nephritis: a multicenter study from southern China.

To investigate the fetal adverse pregnancy outcomes (APOs) and the predictive value of umbilical arterial Doppler ultrasonography in the third trimester in pregnant women with lupus nephritis (LN). A retrospective cohort study enrolling 203 LN patients from 2007 to 2017 was performed. Ultrasonic parameters were recorded. Fetal APOs occurred in 103 patients (103/203, 50.7%). Sixty-six pregnancies (66/203, 32.5%) ended with preterm births. The incidence rate of intrauterine growth restriction (IUGR) was 18.2% (37/203). Fetal distress was noted in 23 pregnancies (23/203, 11.3%). All the Doppler parameters elevated in patients with IUGR, fetal distress, and composite conditions. Resistance index (RI) indicated the highest risk of IUGR and composite APOs. The cutoff values were 0.66 and 0.67, respectively. Sensitivities were 51.4% and 33.7%, and specificities were 87.4% and 92.1%. Peak velocity of the umbilical arteries at end-systole (Vmax, abbreviated as S) to that at end-diastole (Vmin, abbreviated as D) (S/D) ratio was also a best predictor for IUGR, with the optimal cutoff value of 2.88. Sensitivity and specificity were comparable with RI. Pulsatility index (PI) over 0.84 was an ideal indicator for fetal distress with an optimal combination of sensitivity (89.5%) and specificity (51.6%). Fetal complications were frequent in patients with LN. Umbilical arterial Doppler ultrasonography was a useful measure to predict late IUGR, fetal distress, and the composite APOs.

Marijuana use in young mothers and adverse pregnancy outcomes: a retrospective cohort study.

To evaluate the association between marijuana use and a composite adverse pregnancy outcome using biological sampling. Retrospective cohort study. Single tertiary center. Young women (13-22years old) with singleton, non-anomalous pregnancies delivered from September 2011 to May 2017. Exposure was defined as marijuana detected on universal urine toxicology testing or by self-report. Multivariable logistic regression modelling was used to estimate the effect of any marijuana use on the primary composite outcome. The effect of marijuana exposure was also estimated for self-reported use, toxicology-detected use, and multiple use detected by toxicology. The primary composite outcome included spontaneous preterm birth, hypertensive disorders of pregnancy, stillbirth, or small for gestational age. Of 1206 pregnant young women, 17.5% (n=211) used marijuana. Among the women who used marijuana, 8.5% (n=18) were identified by self-report alone, 63% (n=133) by urine toxicology alone, and 28.4% (n=60) by both. Urine toxicology testing results were available for 1092 (90.5%) births. The composite outcome occurred more frequently in pregnancies exposed to marijuana (46 versus 34%, P<0.001). This remained significant after adjusting for race/ethnicity and tobacco in the multivariable model (adjusted OR 1.50, 95%CI 1.09-2.05). When marijuana exposure was defined by self-report only, the association with adverse pregnancy outcome became non-significant (adjusted OR 1.01, 95%CI 0.62-1.64). In a population of young women with nearly universal biological sampling, marijuana exposure was associated with adverse pregnancy outcomes. The heterogeneity of findings in existing studies evaluating the impact of marijuana on mothers and neonates may result from the incomplete ascertainment of exposure. Marijuana use, as detected by universal urine testing, was associated with a composite adverse pregnancy outcome among young mothers.

Predicting Intrauterine Transfusion Interval and Perinatal Outcomes in Alloimmunized Pregnancies: Time-to-Event Survival Analysis

Background: The risk factors determining the frequency of intrauterine transfusions (IUTs) for severely affected red blood cell alloimmunized singleton pregnancies are not well known. Objective: To assess factors associated with IUT frequency and adverse pregnancy outcomes in transfused pregnancies.Methods: Retrospective cohort analysis of 246 consecutive cases between 1991 and 2014. Time-to-event survival analysis for repeated events was used to evaluate risk of subsequent IUT. Multivariable logistic regression assessed odds of a composite adverse pregnancy outcome (intrauterine fetal death, termination of pregnancy, neonatal death, preterm birth <34 weeks’ gestation). Results: Full information was available on232 cases (94.3%) and 716 IUTs. Fetal hydrops was associated with increased frequency (hazard ratio [HR] 1.29 [95% CIs 1.15–1.47, p < 0.001]) while higher fetal hemoglobin (Hb) pre-IUT (HR) 0.99 (95% CI 0.99–1.00, p = 0.021) and post-IUT (HR 0.99 [95% CI 0.99–1.00] p = 0.042), and higher transfused blood volume (HR 0.98 [95% CI 0.97–0.99] p < 0.001) were associated with reduced IUT frequency. Adverse pregnancy outcomes were more likely with lower gestational age (GA) at initial IUT. Antibody type was not associated with IUT frequency or adverse pregnancy outcomes. Conclusions: Hydrops is associated with increased IUT frequency while lower GA at initial IUT is associated with higher adverse pregnancy outcomes in alloimmunized pregnancies.Higher transfused blood volumes, pre- and post-IUT Hb are associated with lower IUT frequency.

Risk of Adverse Pregnancy Outcomes at Advanced Maternal Age

(Obstet Gynecol 2018;131:457–463) Previous studies examining associations between advanced maternal age and adverse pregnancy outcomes have conflicting findings, are inadequately powered, or are prone to bias. The authors of the present study thereby examined the possible associations between advanced maternal age (above 35 y of age) and adverse pregnancy outcomes in a large population-based cohort of pregnant women in Denmark, followed from first trimester to delivery or termination of pregnancy. The authors also predicted risk estimates of a composite adverse pregnancy outcome, to identify whether certain groups of parturients are at risk for select adverse pregnancy outcomes.

49: Marijuana use and adverse perinatal outcomes in young mothers

Self-report underestimates drug use, which may affect the validity of existing studies reporting on pregnancy outcomes with marijuana (MJ) exposure. We aimed to evaluate the association between MJ use and adverse pregnancy outcomes in a population with universal biologic sampling. Retrospective cohort study of all mothers in an adolescent maternity program (13-22 years old) with singleton, non-anomalous pregnancies who delivered at a single tertiary center (Sept 2011-May 2017). Adolescents are screened universally with urine toxicology (utox) at the first prenatal visit. Exposure was defined as MJ detected on utox or by self-report on a uniformly administered questionnaire. The primary composite outcome included spontaneous preterm birth, hypertensive disorders of pregnancy, stillbirth, or small for gestational age. A sample size of 1200 was calculated to have 80% power to detect a difference in the rate of the composite outcome of 8% assuming a MJ use prevalence of 18%. Demographic and clinical characteristics were compared using t-tests or χ2. A multivariable model estimated the effect of MJ use on the primary outcome adjusting for race/ethnicity. Other covariates considered for inclusion were age, tobacco use, other illicit substances, history of psychiatric disorder, and a maternal stress score. Of 1206 included births, overall 17% (n=204) were exposed to MJ. Self-report identified 6% and utox 16%. Utox results were available for 91% of births. For others, utox was ordered but not completed. Demographics differed between exposed and unexposed (Table 1). The primary composite outcome occurred more frequently in adolescents who used MJ (46 vs 34%, p<0.001) (Table 2). In multivariable modeling adjusting for race/ethnicity, MJ use was associated with the composite adverse outcome (OR 1.53, 95% CI 1.12-2.09). After excluding 114 adolescents without utox results, odds of the composite adverse outcome increased slightly (OR 1.73, 95% CI 1.25-2.39). In a population with nearly universal biologic sampling, marijuana use was associated with a composite adverse pregnancy outcome including spontaneous preterm birth, hypertensive disorders of pregnancy, stillbirth, or small for gestational age. Uncertainty regarding the impact of MJ on pregnancy outcomes in the literature may result from incomplete ascertainment of exposure.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Magnitude of change in fetal cerebroplacental ratio in third trimester and risk of adverse pregnancy outcome.

To evaluate whether the magnitude of change in the cerebroplacental ratio (CPR) after 30 weeks' gestation is a better predictor of adverse pregnancy outcome compared with a single CPR measurement at 35-37 weeks. A secondary aim was to evaluate whether the utility of CPR at 35-37 weeks was enhanced after adjusting for change in gestational age. This was a retrospective cohort study of women who had at least two ultrasound scans between 30 and 37 weeks' gestation, with the final scan at 35-37 weeks. Exclusion criteria were major congenital abnormality, aneuploidy, multiple pregnancy and unknown middle cerebral artery pulsatility index or umbilical artery pulsatility index. A normal reference range for CPR was derived from a separate cohort of women with normal outcome and a Generalised Additive Model for Location, Scale and Shape was fitted to derive standardized centiles. These reference centiles were then used to calculate Z-scores for the study cohort. Logistic regression models and receiver-operating characteristics (ROC) curves were used to evaluate the predictive utility of CPR Z-score at last CPR measurement and the change in CPR on mode of delivery, neonatal outcome and composite neonatal outcome. The area under the ROC curve (AUC) for each model was compared before and after adjustment for parity, hypertension, diabetes, body mass index and smoking status. A total of 1860 women met the inclusion criteria. There was no association between the magnitude of change in CPR and composite adverse pregnancy outcome (P = 0.92). Of the outcomes that made up the composite, an increase in CPR Z-score over time was associated with a lower risk for emergency Cesarean delivery (P < 0.001) and emergency Cesarean delivery for non-reassuring fetal status (P = 0.02). It was also associated with a lower risk of birth weight < 10th centile (P = 0.01) and hypoglycemia (P = 0.001). There was no significant difference between the AUCs of last CPR Z-score and last CPR Z-score adjusted for the change in gestational age in predicting pregnancies at risk for adverse outcome. Our results suggest that both the individual CPR Z-score and the magnitude and direction of change in CPR Z-score can identify pregnancies at risk of various adverse perinatal outcomes. However, the CPR Z-score at 35-37 weeks' gestation appears to be a better predictor. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

P29.05: Placental cord insertion site and adverse pregnancy outcome in twin pregnancy

Abnormal umbilical cord insertion has been associated with unequal sharing of the placental vasculature between twins. A higher prevalence has been reported in pregnancies complicated by selective growth restriction (sFGR), birth weight discordance (BWD). We aimed to investigate the association between cord insertion site and adverse pregnancy outcomes in twin pregnancies. A single-centre cohort study of twin pregnancies that had placental histology. Higher-order multiples, major fetal anomaly, aneuploidy and MCMA pregnancies were excluded. Cord insertion site was categorised into 3 groups: marginal (attachment <2cm to the placental margin), velamentous (attached to the membrane before reaching the placenta with vessels traversing the membranes), normal. Chorionicity, placental weight, number of cord vessels, examination of the membranes, ultrasound findings, maternal characteristics and pregnancy outcome were collected. 546 pregnancies were eligible; 497 (146 monochorionic; 351 dichorionic) were included in the analysis. Significant differences were found between the normal and abnormal cord insertion groups with regards to BWD (P=0.001), BWD>25% (P=0.001), and absolute Z-score differences (P=0.020). Velamentous, but not marginal, cord insertion was significantly associated with sFGR (OR 8.51,95%CI 2.09-34.58;P=0.03) and BWD>25% (OR 11.88,95%CI 3.54-39.79;P=0.04). In MCDA, but not DCDA pregnancies, the rate of composite adverse outcome was higher in those with abnormal cord insertion (70.0% vs 53.0%, p=0.04). Selective fetal growth restriction and birthweight discordance are more common in twin pregnancies with abnormal cord insertion. MCDA twins with velamentous cord insertion are at increased risk of sFGR, and composite adverse pregnancy outcome.

Maternal marijuana use, adverse pregnancy outcomes, and neonatal morbidity

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Stillbirth Collaborative Research Network previously demonstrated an association between stillbirth and maternal marijuana use as defined by the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in the umbilical cord homogenate. However, the relationship between marijuana use and perinatal complications in live births is uncertain. Our aim was to examine if maternal marijuana use is associated with increased odds of adverse pregnancy outcomes and neonatal morbidity among live-born controls in the Stillbirth Collaborative Research Network cohort. We conducted a secondary analysis of singleton, live-born controls in the Stillbirth Collaborative Research Network data set. Marijuana use was measured by self-report and/or the presence of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in umbilical cord homogenate. Tobacco use was measured by self-report and/or presence of any cotinine in maternal serum. Adverse pregnancy outcome was a composite of small for gestational age, spontaneous preterm birth resulting from preterm labor with or without intact membranes, and hypertensive disorders of pregnancy. Neonatal morbidity included neonatal intensive care unit admission and composite neonatal morbidity (pulmonary morbidity, necrotizing enterocolitis, seizures, retinopathy of prematurity, infection morbidity, anemia requiring blood transfusion, neonatal surgery, hyperbilirubinemia, neurological morbidity, or death prior to hospital discharge). Effect of maternal marijuana use on the probability of an adverse outcome was estimated using weighted methodology to account for oversampling in the original study. 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid cord homogenate analysis was performed in the subset of women for whom biospecimens were available. Comparisons using logistic modeling, χ2, and t tests were weighted to account for oversampling of preterm births and non-Hispanic blacks. Results are reported as weighted percent and unweighted frequencies. Maternal marijuana use was identified in 2.7% (unweighted frequency 48/1610) of live births. Use was self-reported by 1.6% (34/1610) and detected by 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in cord homogenate for 1.9% (17/897), n= 3 overlapping. Rate of tobacco use was 12.9% (217/1610), with 10.7% (167/1607) by self-report and 9.5% (141/1313) by serum cotinine. The composite adverse pregnancy outcome was not significantly increased in women with marijuana use compared to nonusers (31.2% vs 21.2%; P= .14). After adjustment for tobacco, clinical, and socioeconomic factors, marijuana use was not associated with the composite adverse pregnancy outcome (adjusted odds ratio, 1.29; 95% confidence interval, 0.56-2.96). Similarly, among women with umbilical cord homogenate and serum cotinine data (n= 765), marijuana use was not associated with adverse pregnancy outcomes (adjusted odds ratio, 1.02; 95% confidence interval, 0.18-5.66). Neonatal intensive care unit admission rates were not statistically different between groups (16.9% users vs 9.5% nonusers, P=.12). Composite neonatal morbidity or death was more frequent among neonates of mothers with marijuana use compared to nonusers (14.1% vs 4.5%; P= .002). In univariate comparisons, the components of the composite outcome that were more frequent in neonates of marijuana users were infection morbidity (9.8% vs 2.4%; P < .001) and neurologic morbidity (1.4% vs 0.3%; P= .002). After adjustment for tobacco, race, and other illicit drug use, marijuana use was still associated with composite neonatal morbidity or death (adjusted odds ratio, 3.11; 95% confidence interval, 1.40-6.91). Maternal marijuana use was not associated with a composite of small for gestational age, spontaneous preterm birth, or hypertensive disorders of pregnancy. However, it was associated with an increased risk of neonatal morbidity.

Twin pregnancies complicated by gestational diabetes mellitus: a single centre cohort study.

In women with a twin pregnancy, to determine the incidence of, risk factors for and outcomes of women with gestational diabetes mellitus, and assess how these have changed with a change in gestational diabetes screening. Retrospective cohort study of women with a twin pregnancy attending an Australian tertiary hospital, 2002-2013. Information on gestational diabetes status, gestational diabetes risk factors and pregnancy outcomes was ascertained. Pregnancy outcomes included hypertensive disorders, twin birthweight centile and a composite adverse pregnancy outcome. Analysis was stratified pre/post screening protocol change (epoch 1: 2002-2009, epoch 2: 2010-2013) and by gestational diabetes status. Gestational diabetes was diagnosed in 86/982 (8.8%) women, increasing from 4.4% to 14.7% between epochs (P = 0.0001). The proportion of women with hypertensive disorders increased (11.7% vs. 13.4%, P = 0.009), but the proportion of infant's birthweight > 90th centile decreased (11.0% vs. 7.6%, P = 0.02) between epochs. Overall, 33.6% of women had ≥ 1 risk factors for gestational diabetes. Three-quarters (73.7%) of women overall had an adverse pregnancy outcome, with a slightly higher proportion in women with gestational diabetes compared with those with no gestational diabetes (79.7% vs. 73.1%, P = 0.06). The rate of the adverse pregnancy outcome did not change by epoch, after adjusting for maternal and pregnancy risk factors (adjusted odds ratio = 0.96, 95% confidence interval 0.73-1.26). Almost 1 in 10 women with a twin pregnancy were diagnosed with gestational diabetes, with the incidence of gestational diabetes increasing threefold with a new screening protocol. The pregnancy outcomes of women with a twin pregnancy did not change with increased detection and treatment for gestational diabetes.

Pregestational diabetes is associated with adverse outcomes in twin pregnancies: a regional register‐based study

The incidence of pregnancies complicated by twinning and diabetes is increasing in the UK. This is a worrying trend as both diabetes and twin gestations are associated with a high risk of adverse pregnancy outcomes. The few studies that have specifically addressed how twinning and pregestational diabetes in the same pregnancy may affect outcome have reported conflicting results. We analyzed data on 27 women with a twin pregnancy and pregestational diabetes (54 babies) and 6407 women with a twin pregnancy without diabetes (12 814 babies) from the Northern Survey of Twin and Multiple Pregnancy during 1998-2010. A composite adverse pregnancy outcome (comprising fetal loss before 24 weeks, termination of pregnancy, stillbirth, infant death or any major congenital anomaly), extended perinatal mortality (stillbirths and neonatal deaths) and major congenital anomaly were the main outcome measures. Adjusted rate ratios were estimated using generalized estimating equations for Poisson regression controlling for potential confounders. Mothers with twin pregnancies with diabetes were older (p = 0.001) and had higher body mass indices (p < 0.0001) than those without diabetes. Their twins were more likely to be delivered earlier (p = 0.026), be delivered by cesarean section (80.4% vs. 49.7%; p < 0.0001), be large-for-gestational-age (p < 0.0001) and require admission to a special care baby unit (p < 0.0001). Pregestational diabetes was associated with significantly increased rates of the composite adverse outcome and major congenital anomalies in twins (adjusted rate ratios 2.66, 95% confidence interval 1.14-6.20 and adjusted rate ratios 3.51, 95% confidence interval 1.31-9.40, respectively). Maternal pregestational diabetes in twin pregnancies is associated with a significantly increased risk of an adverse pregnancy outcome.

Doppler Audio Signal Analysis as an Additional Tool in Evaluation of Umbilical Artery Circulation

Purpose To investigate the predictive capacity of a new method for sound spectrum analysis of Doppler signals recorded from the umbilical artery in high-risk pregnancies. Material and Methods The retrospective study comprised 127 pregnant women with various pregnancy complications between 23 and 39 gestational weeks. Umbilical artery blood flow velocity waveforms were recorded with Doppler ultrasound and characterized by pulsatility index (PI) and blood flow class (BFC). Doppler audio signals were stored on a digital video recorder and the sound frequency at the energy level 15 dB below its peak (MAXpeak-15 dB) was estimated off-line. The prediction of probability for composite adverse pregnancy outcome (operative delivery for fetal distress, admission to neonatal intensive care unit, perinatal death) was evaluated using the area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results With increasing umbilical artery BFC, the MAXpeak-15 dB frequencies decreased (p < 0.0001) and the PI increased (p < 0.0001). The ROC AUCs for adverse outcome for MAXpeak-15 dB and for PI were 0.842 and 0.836 (p = 0.88), respectively. For the combination of MAXpeak-15 dB and PI, the corresponding AUC was 0.894, significantly higher than that of PI (p < 0.03) and of MAXpeak-15 dB (p < 0.05). Conclusion Umbilical artery Doppler sound spectrum analysis might be a useful supplement to PI in the clinical evaluation of fetoplacental circulation.

Vitamin D deficiency in early pregnancy.

ObjectiveVitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.Study DesignThis is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.ResultsVitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years). Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL). Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057).ConclusionVitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

Evaluation of anti‐Mullerian hormone in the first trimester as a predictor for hypertensive disorders of pregnancy and other adverse pregnancy outcomes

Prediction of pre-eclampsia and adverse pregnancy outcomes with biomarkers has been proposed. AMH is an ovary-specific growth factor, used to predict ovarian reserve, which changes with age similar to the change in age-related fertility. The aim of the study was to determine whether AMH tested in the first trimester of pregnancy was associated with pregnancy hypertension or adverse pregnancy outcomes. Retrospective cohort study of women who delivered singleton fetuses ≥20 weeks' gestation at Royal Hospital for Women, Sydney, Australia (n = 331). AMH was tested in 2011 via Beckman-Coulter Gen II ELISA method on frozen serum collected at the time of first trimester aneuploidy screening (10-13 + 6 weeks' gestation). Outcome data were obtained from the hospital database (ObstetriX). Main outcome measures were pregnancy hypertension (pre-eclampsia and gestational hypertension) and composite adverse pregnancy outcome. The median AMH level was 9.7 pmol/L (interquartile range (IQR) 3.9-17.3). There was a trend towards women with pregnancy hypertension having lower AMH levels than women without pregnancy hypertension (median 5.1 pmol/L, IQR 1.5-13.2 vs 9.4 IQR 3.9-17.3; P = 0.06). After adjusting for BMI ≥25, parity ≥1 and age ≥35, women with an AMH less than the 10th centile had a 3.3-fold increased risk of pregnancy hypertension (OR 3.3, 95% CI 1.2-8.7, P = 0.01). There were no other associations between low AMH concentration and adverse maternal or neonatal outcomes. Women with a very low AMH (1.5 pmol/L) in early pregnancy may have an increased risk of pregnancy hypertension. No other adverse pregnancy outcomes were identified.