Pregnancy Outcomes in Women With Multiple Sclerosis.

Few studies have assessed the risk of adverse pregnancy outcomes in women with multiple sclerosis (MS). We used 2 large US administrative databases, the Truven Health MarketScan Database (2011-2015; Truven Health Analytics Inc., Ann Arbor, Michigan) and the Nationwide Inpatient Sample (2007-2011), to identify delivery cohorts. MS and pregnancy outcomes (infections, cesarean delivery, preterm delivery, poor fetal growth, preeclampsia, chorioamnionitis, postpartum hemorrhage, stillbirth, and infant malformations) were identified during pregnancy and at delivery. We calculated adjusted risk ratios according to MS status and relapse(s) in the year before delivery. Among over 5 million pregnancies, we identified 3,875 pregnancies in women with MS. Women with MS had an increased risk of infections during pregnancy (Truven Health: adjusted risk ratio (aRR) = 1.22, 95% confidence interval (CI): 1.16, 1.27) and preterm delivery (Truven Health: aRR = 1.19 (95% CI: 1.04, 1.35); Nationwide Inpatient Sample: aRR = 1.30 (95% CI: 1.16, 1.44)). The risks of other outcomes were similar for women with and without MS. In the Truven Health database, risk ratios for the pregnancy outcomes in women experiencing relapses versus those without relapses were between 0.9 and 1.4, and confidence intervals overlapped the null. Overall, women with MS had an increased risk of infections and preterm delivery; however, their risks for other adverse pregnancy outcomes were not elevated. Disease activity before delivery was not a strong predictor of outcomes.

Use and safety of disease-modifying therapy in pregnant women with multiple sclerosis.

PURPOSE: The purpose of this study is to describe dispensing patterns and comparative safety of disease-modifying therapies (DMTs) during pregnancy in women with multiple sclerosis (MS). METHODS: We identified pregnancies from the Truven Health Marketscan® Commercial Claims and Encounters Database (2011-2015) and ascertained MS before delivery from inpatient and outpatient claims. We computed the proportion of women with DMT dispensing claims around pregnancy and estimated risk ratios of spontaneous abortion, infections, cesarean section, preterm delivery, poor fetal growth, preeclampsia, and major structural malformations by DMT exposure. RESULTS: Of 984 058 pregnancies, 1649 were to women with MS. Thirty-five percent of women with MS filled a prescription for a DMT in the 90 days before pregnancy. DMT use declined during pregnancy but increased again after delivery. Glatiramer acetate and interferon beta were most commonly dispensed. Pregnancies with and without early DMT exposure had similar risks of outcomes to one another and to pregnancies in women without MS. Small numbers did not allow evaluation of specific DMTs. CONCLUSIONS: Approximately one third of commercially insured women with MS in the United States uses DMTs before conception. Neither MS itself nor early pregnancy use of DMTs overall seems to be associated with a substantial risk of adverse pregnancy outcomes.

Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance.

PURPOSE: The purpose of the study is to develop an algorithm to identify pregnancies in administrative databases and apply it to assess pregnancy rates and outcomes in women prescribed isotretinoin or tretinoin. METHODS: Using the 2011 to 2015 Truven Health MarketScan Database, we identified pregnancies, including losses and terminations. In a cohort design, nonpregnant women filling a prescription for isotretinoin or tretinoin were matched to five women without either prescription. Women were followed for 365 days or until conception, medication discontinuation, or enrollment discontinuation ("prescription episode"). Rates of pregnancy, risks of pregnancy losses, and prevalence of infant malformations at birth were assessed by exposure. RESULTS: We identified 2 179 192 livebirths, 8434 stillbirths, 2521 mixed births, 415 110 spontaneous abortions, 124 556 elective terminations, and 8974 unspecified abortions. There were 86 834 isotretinoin and 973 587 tretinoin episodes, matched to 5 302 105 unexposed women. Pregnancy rates were 3 (isotretinoin), 19 (tretinoin), and 34 (unexposed) per 1000 person-years. Risk of spontaneous pregnancy losses were similar; however, terminations were more common in the isotretinoin-exposed (28% [95% CI: 21%-36%]) than the tretinoin-exposed (10% [95% CI: 9%-11%]) or unexposed pregnancies (6%). Malformations occurred in 4.5% (95% CI: 3.5%-5.6%) of the tretinoin-exposed pregnancies and 4.2% of the unexposed pregnancies (adjusted odds ratio: 1.16 [95% CI: 0.85-1.58]); isotretinoin-exposed births were too few to assess malformations. CONCLUSIONS: Administrative databases can complement risk evaluation and mitigation strategies (REMS) for known teratogens and contribute to safety surveillance for other medications. Here, isotretinoin-exposed pregnancy rates were low, but existent, and many pregnancies were terminated. Tretinoin exposure was not associated with a meaningfully elevated risk of losses or malformations as compared with unexposed pregnancies.

Assessment of recording bias in pregnancy studies using health care databases: An application to neurologic conditions.

BACKGROUND: Pre-existing conditions are imperfectly recorded in health care databases. We assessed whether pre-existing neurologic conditions (epilepsy, multiple sclerosis [MS]) were differentially recorded in the presence of major obstetric outcomes (Caesarean delivery, preterm delivery, preeclampsia) in delivery records. We also evaluated the impact of differential recording on measures of frequency and association between the conditions and outcomes. METHODS: The 2011-2014 Truven Health MarketScan® Commercial Claims Dataset was used to identify pregnancies. We calculated the relative recording of epilepsy and MS at delivery hospitalization compared with a 270-day pre-delivery window both overall and by the presence of major obstetric outcomes. We estimated risk ratios for the association between epilepsy and MS with the outcomes for each ascertainment window. RESULTS: We identified 909 065 pregnancies in women continuously enrolled from 270-days before the delivery date. Of women with epilepsy identified in the pre-delivery window, 73% had the condition coded at delivery. For MS, the proportion was 60%. MS recording at delivery did not vary by obstetric outcomes, however, delivery-coded epilepsy was less likely confirmed in the pre-delivery window in the presence of preeclampsia. Generally, the period of ascertainment did not meaningfully impact risk ratios, however, the risk ratio for preeclampsia associated with epilepsy was 1.67 (95% CI 1.47, 1.90) when epilepsy was ascertained at delivery and 1.26 (95% CI 1.07, 1.48) when epilepsy was ascertained in the pre-delivery window (heterogeneity, P = .007). CONCLUSIONS: Ascertainment of epilepsy and MS in delivery hospitalization records underestimated prevalence. However, the window of recording generally did not impact risk ratio estimates of associations with obstetric outcomes.

Patterns of Gestational Weight Gain in Early Pregnancy and Risk of Gestational Diabetes Mellitus.

BACKGROUND: Despite a call to study the effect of weight gain pattern on development of gestational diabetes mellitus, few studies have correctly adjusted for independent effects of gain after the first trimester. We used a conditional percentile approach to model the independent association between first and second trimester weight gain trajectories and development of gestational diabetes. METHODS: We sampled women delivering singleton infants from 1998 to 2010 at Magee-Womens Hospital in Pittsburgh, PA, (n = 124,590) using a case-cohort design. We modeled weight gain trajectories in the first and second trimesters of pregnancy using conditional weight gain percentiles, and used multivariable logistic regression to assess independent associations of the trajectory with gestational diabetes. We studied associations separately by prepregnancy body mass index category. RESULTS: The final cohort included 806 women with gestational diabetes and 4,819 randomly sampled women who delivered without gestational diabetes. In normal-weight women, every SD increase in weight gain in the first trimester above her predicted gain was associated with a 23% increased odds of gestational diabetes (95% confidence interval: 0.2%, 51%). Second trimester gain trajectory was not associated with gestational diabetes (odds ratio: 1.1, [95% confidence interval: 0.9, 1.3]) although the direction of effect was positive. This pattern was similar in obese class I and II but not in overweight and obese class III women. CONCLUSIONS: An upward weight gain trajectory in the first trimester was positively associated with gestational diabetes for women of most prepregnancy BMI categories. Second trimester weight gain trajectory was not associated with gestational diabetes for any group.

Delivery planning for pregnancies with gastroschisis: findings from a prospective national registry.

OBJECTIVE: The purpose of this study was to determine the influence of planned mode and planned timing of delivery on neonatal outcomes in infants with gastroschisis. STUDY DESIGN: Data from the Canadian Pediatric Surgery Network cohort were used to identify 519 fetuses with isolated gastroschisis who were delivered at all tertiary-level perinatal centers in Canada from 2005-2013 (n = 16). Neonatal outcomes (including length of stay, duration of total parenteral nutrition, and a composite of perinatal death or prolonged exclusive total parenteral nutrition) were compared according to the 32-week gestation planned mode and timing of delivery with the use of the multivariable quantile and logistic regression. RESULTS: Planned induction of labor was not associated with decreased length of stay (adjusted median difference, -2.6 days; 95% confidence interval [CI], -9.9 to 4.8), total parenteral nutrition duration (adjusted median difference, -0.2 days; 95% CI, -6.4 to 6.0), or risk of the composite adverse outcome (relative risk, 1.7; 95% CI, 0.1-3.2) compared with planned vaginal delivery after spontaneous onset of labor. Planned delivery at 36-37 weeks' gestation was not associated with decreased length of stay (adjusted median difference, 5.9 days; 95% CI, -5.7 to 17.5), total parenteral nutrition duration (adjusted median difference, 3.2 days; 95% CI, -7.9 to 14.3), or risk of composite outcome (relative risk, 2.3; 95% CI, 0.8-5.4) compared with planned delivery at ≥38 weeks' gestation. CONCLUSION: Infants with gastroschisis who were delivered after planned induction or planned delivery at 36-37 weeks' gestation did not have significantly better neonatal outcomes than planned vaginal delivery after spontaneous onset of labor and planned delivery at ≥38 weeks' gestation.

Frequency of Opioid Dispensing After Vaginal Delivery.

OBJECTIVE: To describe nationwide patterns in outpatient opioid dispensing after vaginal delivery. METHODS: Using the Truven Health Analytics MarketScan database, we performed a large, nationwide retrospective cohort study of commercially insured beneficiaries who underwent vaginal delivery between 2003 and 2015 and who were opioid-naive for 12 weeks before the delivery admission. We assessed the proportion of women dispensed an oral opioid within 1 week of discharge, the associated median oral morphine milligram equivalent dose dispensed, and the frequency of opioid refills during the 6 weeks after discharge. We evaluated predictors of opioid dispensing using multivariable logistic regression. RESULTS: Among 1,345,244 women undergoing vaginal delivery, 28.5% were dispensed an opioid within 1 week of discharge. The most commonly dispensed opioids were hydrocodone (44.7%), oxycodone (34.6%), and codeine (13.1%). The odds of filling an opioid were higher among those using benzodiazepines (adjusted odds ratio [OR] 1.87, 95% CI 1.73-2.02) and antidepressants (adjusted OR 1.63, 95% CI 1.59-1.66), smokers (adjusted OR 1.44, 95% CI 1.38-1.51), and among those undergoing tubal ligation (adjusted OR 3.77, 95% CI 3.67-3.87), operative vaginal delivery (adjusted OR 1.52, 95% CI 1.49-1.54), and higher order perineal laceration (adjusted OR 2.15, 95% CI 2.11-2.18). The median (interquartile range, 10th-90th percentile) dose of opioids dispensed was 150 (113-225, 80-345) morphine milligram equivalents, equivalent to 20 tablets (interquartile range 15-30, 10th-90th percentile 11-46) of 5 mg oxycodone. Six weeks after discharge, 8.5% of women filled one or more additional opioid prescriptions. CONCLUSION: Opioid dispensing after vaginal delivery is common and often occurs at high doses. Given the frequency of vaginal delivery, this may represent an important source of overprescription of opioids in the United States.

Pregabalin use early in pregnancy and the risk of major congenital malformations.

OBJECTIVE: To assess whether first-trimester exposure to pregabalin is associated with an increased risk of major congenital malformations, as recently suggested in a pregnancy registry study. METHODS: We performed a cohort study nested in the US Medicaid Analytic eXtract (MAX). The study population included 1,323,432 pregnancies resulting in a live-born infant between 2000 and 2010. We examined the risk of major congenital malformations among infants born to women exposed to pregabalin during the first trimester compared with women unexposed to anticonvulsants. We used propensity score fine stratification to control for >50 potential confounders, and we estimated relative risks (RRs) and 95% confidence intervals (CIs) in generalized linear models. The analyses were replicated in the Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based on the adjusted RR produced in MAX, MarketScan, and the previous registry study were calculated. RESULTS: Of 477 infants exposed to pregabalin during the first trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed infants. The crude RR of major congenital malformations for pregabalin was 1.80 (95% CI 1.26-2.58). After propensity score adjustment, the RR moved to 1.16 (95% CI 0.81-1.67). Restriction to pregabalin monotherapy and sensitivity analyses produced similar results. The adjusted RR for major congenital malformations for the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56-1.90). The pooled RR was 1.33 (95% CI 0.83-2.15) for pregabalin any use and 1.02 (95% CI 0.69-1.51) for pregabalin monotherapy. CONCLUSIONS: Findings did not confirm the suggested teratogenic effects of pregabalin, although they cannot rule out the possibility of a small effect.

Use of atypical antipsychotics in pregnancy and maternal gestational diabetes.

BACKGROUND: Second generation antipsychotic medications (SGAs) are widely used by reproductive-age women to treat a number of psychiatric illnesses. Some SGAs have been associated with an increased risk of developing diabetes, although information regarding their diabetogenic effect in pregnant women is scarce. OBJECTIVE: To evaluate the risk of gestational diabetes (GDM) among women treated with SGA. METHOD: The Massachusetts General Hospital (MGH) National Pregnancy Registry for Atypical Antipsychotics (NPRAA) collects data on drug use, pregnancy outcomes, and other characteristics from pregnant women, ages 18-45 years, using 3 phone interviews conducted at (1) enrollment during pregnancy, (2) 7 months' gestation, and (3) 2-3 months postpartum. Information on GDM was abstracted from obstetric and delivery medical records. The study population was restricted to women without pre-gestational diabetes. Pregnancies exposed to SGAs during the first trimester were compared with a reference group of women with psychiatric conditions but not treated with SGAs during pregnancy. Generalized linear models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for GDM. RESULTS: Of 303 women exposed to SGAs, 33 (10.9%) had GDM compared to 16 (10.7%) in the 149 non-exposed women. The crude OR of GDM for SGA was 1.02 (95% CI, 0.54-1.91). After adjustment for maternal age, race, marital status, employment status, level of education, smoking, and primary psychiatric diagnosis, the OR moved to 0.79 (0.40-1.56). CONCLUSIONS: Findings did not suggest an increased risk of GDM associated with exposure to SGAs during pregnancy in women who had used SGA before pregnancy without developing diabetes, compared to psychiatrically ill women who were not exposed to SGA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01246765.

Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States.

IMPORTANCE: Between 0.3% and 0.5% of all pregnancies occur among women with epilepsy. Evidence suggests an increase in perinatal morbidity and mortality among women with epilepsy. However, these risks have not been quantified in large population-based samples. OBJECTIVE: To report on the risk for death and adverse outcomes at the time of delivery for women with epilepsy in the United States. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007-2011 Nationwide Inpatient Sample. From this representative sample of 20% of all US hospitals, we obtained a weighted sample of delivery hospitalizations from 69 385 women with epilepsy and 20 449 532 women without epilepsy. MAIN OUTCOMES AND MEASURES: Obstetrical outcomes including maternal death, cesarean delivery, length of stay, preeclampsia, preterm labor, and stillbirth. RESULTS: Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100 000 pregnancies, significantly higher than the 6 deaths per 100 000 pregnancies found among women without epilepsy (adjusted odds ratio [OR], 11.46 [95% CI, 8.64-15.19]). Women with epilepsy were also at a heightened risk for other adverse outcomes, including preeclampsia (adjusted OR, 1.59 [95% CI, 1.54-1.63]), preterm labor (adjusted OR, 1.54 [95% CI, 1.50-1.57]), and stillbirth (adjusted OR, 1.27 [95% CI, 1.17-1.38]), and had increased health care utilization, including an increased risk of cesarean delivery (adjusted OR, 1.40 [95% CI, 1.38-1.42]) and prolonged length of hospital stay (>6 days) among both women with cesarean deliveries (adjusted OR, 2.13 [95% CI, 2.03-2.23]) and women with vaginal deliveries (adjusted OR, 2.60 [95% CI, 2.41-2.80]). CONCLUSIONS AND RELEVANCE: Findings suggest that women with epilepsy are at considerably heightened risk for many adverse outcomes during their delivery hospitalization, including a more than 10-fold increased risk of death, and that increased clinical attention is imperative for these pregnancies.

The role of clarity and blur in guiding visual attention in photographs.

Visual artists and photographers believe that a viewer's gaze can be guided by selective use of image clarity and blur, but there is little systematic research. In this study, participants performed several eye-tracking tasks with the same naturalistic photographs, including recognition memory for the entire photo, as well as recognition memory and personality ratings for individual people in the photos (Experiments 1-3). The results showed that fixations occurred more rapidly and frequently to a local region of clarity than to a comparable blurred region in all tasks, independent of the content of the photo in the local region, and even under instructions to look equally at both regions. However, this bias was reversed when the content of the photos was no longer task-relevant. In Experiment 4, participants located target regions defined by either clarity or blur. Fixations and manual responses were faster for blurred than for sharp targets. These findings imply that the saliency of both image clarity and image blur depends on viewers' goals. Focusing on photo content prioritizes regions of clarity whereas focusing on photo quality prioritizes attention to regions of blur.