Publications by authors named "Sonia Hernandez-Diaz"

276 Publications

Response to Invited Commentary: Intermittent opioid use and ischemic placental disease: study quantifies risks, raises questions.

Am J Epidemiol 2021 Sep 15. Epub 2021 Sep 15.

Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics, Boston, Massachusetts, United States.

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http://dx.doi.org/10.1093/aje/kwab226DOI Listing
September 2021

Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy.

Nat Med 2021 Sep 7. Epub 2021 Sep 7.

Clalit Research Institute, Innovation Division, Clalit Health Services, Tel Aviv, Israel.

To evaluate the effectiveness of the BNT162b2 messenger RNA vaccine in pregnant women, we conducted an observational cohort study of pregnant women aged 16 years or older, with no history of SARS-CoV-2, who were vaccinated between 20 December 2020 and 3 June 2021. A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56 d after the second dose was 96% (95% confidence interval 89-100%) for any documented infection, 97% (91-100%) for infections with documented symptoms and 89% (43-100%) for COVID-19-related hospitalization. Only one event of severe illness was observed in the unvaccinated group and no deaths were observed in either group. In summary, the BNT162b2 mRNA vaccine was estimated to have high vaccine effectiveness in pregnant women, which is similar to the effectiveness estimated in the general population.
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http://dx.doi.org/10.1038/s41591-021-01490-8DOI Listing
September 2021

Further Observations on Pregnancy Complications and COVID-19 Infection.

JAMA Pediatr 2021 Aug 16. Epub 2021 Aug 16.

Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamapediatrics.2021.2609DOI Listing
August 2021

Reproductive Safety of Second-Generation Antipsychotics: Updated Data From the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

J Clin Psychiatry 2021 Aug 3;82(4). Epub 2021 Aug 3.

Massachusetts General Hospital, Ammon-Pinizzotto Center for Women's Mental Health, Boston, Massachusetts.

Second-generation antipsychotics (SGAs) are prescribed for a wide range of indications in women of reproductive age. The National Pregnancy Registry for Atypical Antipsychotics (NPRAA) was established to determine the risk of major malformations among infants exposed to these medications during the first trimester relative to a comparison group of unexposed infants of mothers with histories of psychiatric morbidity.

Women, aged 18-45 years, with histories of psychiatric illness were prospectively followed through pregnancy and during the postpartum period. Pediatric and maternal medical records were obtained and screened for evidence of major malformations. Potential cases were adjudicated by a dysmorphologist who was blinded to drug exposure.. Recruitment to the Registry, which is based at the Ammon-Pinizzotto Center for Women's Mental Health at Massachusetts General Hospital (MGH), includes nationwide provider referral, self-referral, and advertisement through the MGH Center for Women's Mental Health website.

As of April 9, 2020, 1,906 women had enrolled, including 889 in the exposure group and 1,017 controls. A total of 1,311 women completed the study and were eligible for inclusion in the analysis. Medical records were obtained for 81.3% of participants. Among 640 live births in the exposure group, 16 (2.50%) had confirmed major malformations reported, and among 704 live births in the control group, 14 (1.99%) had confirmed major malformations reported. The estimated odds ratio for major malformations comparing exposed and unexposed infants was 1.48 (95% CI, 0.625-3.517).

Data from the Registry assessing SGAs as a class indicate that they are unlikely to have a major teratogenic effect. These findings provide pertinent information for women and their health care providers regarding decisions about atypical antipsychotic use during pregnancy.

ClinicalTrails.gov identifier: NCT01246765.
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http://dx.doi.org/10.4088/JCP.20m13745DOI Listing
August 2021

Validation of a claims-based algorithm to identify pregestational diabetes among pregnant women in the United States.

Epidemiology 2021 Jun 25. Epub 2021 Jun 25.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, USA. Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA. Division of Maternal-Fetal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA. Endocrinology, Diabetes and Hypertension Division, Brigham and Women's Hospital and Harvard Medical School.

Background: Identifying pregestational diabetes in pregnant women using administrative claims databases is important for studies of the safety of antidiabetic treatment in pregnancy, but limited data are available on the validity of case-identifying algorithms. The purpose of this study was to evaluate the validity of an administrative claims-based algorithm to identify pregestational diabetes.

Methods: Using a cohort of pregnant women nested within the Medicaid Analytic Extract (MAX) database, we developed an algorithm to identify pregestational type 1 and type 2 diabetes mellitus, distinct from gestational diabetes. Within a single large healthcare system in the Boston area, we identified women who delivered an infant between 2000 and 2010 and were covered by Medicaid, and linked their electronic health records to their Medicaid claims within MAX. Medical records were reviewed by two physicians blinded to the algorithm classification to confirm or rule out pregestational diabetes, with disagreements resolved by discussion. We calculated positive predictive values with 95% confidence intervals using the medical record as the reference standard.

Results: We identified 49 pregnancies classified by the claims-based algorithm as pregestational diabetes that were linked to the electronic health records and had records available for review. The PPV for any pregestational diabetes was 92% (95% CI 82 to 97%), type 2 diabetes 87% (68 to 95%), and type 1 diabetes 57% (37 to 75%).

Conclusions: The claims-based algorithm for pregestational diabetes and type 2 diabetes performed well; however, the PPV was low for type 1 diabetes.
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http://dx.doi.org/10.1097/EDE.0000000000001397DOI Listing
June 2021

Assisted Reproductive Techniques, ADHD, and School Performance.

Pediatrics 2021 Jul 25;148(1). Epub 2021 Jun 25.

Departments of Medical Epidemiology and Biostatistics and

Objectives: To examine the long-term impact of assisted reproductive techniques (ART) on offspring neurodevelopment, accounting for parental factors and the role of infertility.

Methods: Linkage of national registers allowed follow-up of >2.4 million children born in Sweden 1986-2012. Information on ART was retrieved from fertility clinics, medical records, and maternal self-report. Attention-deficit/hyperactivity disorder (ADHD) was identified from specialist diagnosis and/or use of medication through 2018. School performance was assessed from records of ninth year final grade averages (0-20) and eligibility for upper secondary school through 2017.

Results: Children conceived with ART had lower risk of ADHD (hazard ratio 0.83; 95% confidence interval [CI]: 0.80 to 0.87) and did better in school (grade mean difference 1.15; 95% CI: 1.09 to 1.21 and eligibility odds ratio 1.53; 95% CI: 1.45 to 1.63) compared with all other children. Differences in parental characteristics explained and even reversed associations, whereas no disadvantage was seen when the comparison was restricted to children of couples with known infertility (adjusted hazard ratio 0.95; 95% CI: 0.90 to 1.00, adjusted mean difference 0.05; 95% CI: -0.01 to 0.11, and adjusted odds ratio 1.03; 95% CI: 0.96 to 1.10). Among children conceived with ART, there was furthermore no indication that intracytoplasmic sperm injection (compared with standard in vitro fertilization) or frozen (compared with fresh) embryo transfer had any adverse influence.

Conclusions: With this nationwide, long-term follow-up, we provide additional reassurance concerning offspring neurodevelopment after use of ART, finding no indication for concern about risk of ADHD or school performance in adolescence.
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http://dx.doi.org/10.1542/peds.2020-033183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276593PMC
July 2021

Ischemic Placental Disease, Preterm Delivery, and their Association with Opioid Use During Pregnancy.

Am J Epidemiol 2021 Jun 24. Epub 2021 Jun 24.

Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics, Boston, Massachusetts, United States.

Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited. Using a cohort of pregnant women in the US nationwide Medicaid Analytic eXtract (2000-2014), we compared women with ≥2 opioid dispensings in pregnancy to unexposed women. Given an uncertain etiologically relevant window, we assessed exposure occurring in early pregnancy, late and not early pregnancy, and both early and late pregnancy. For placental abruption, preterm delivery, small for gestational age (SGA), and preeclampsia, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusting for demographics, indications/comorbidities, and medications. Of 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled by 6.5%. We observed an early exposure aHR of 1.34 (95% CI 1.26-1.43) for placental abruption, 1.21 (1.18-1.23) for preterm delivery, 1.13 (1.09-1.17) for SGA, and 0.95 (0.91-0.98) for preeclampsia. Estimates for late exposure were attenuated. Early and late exposure was associated with higher aHRs for placental abruption (1.62, 1.47-1.78), preterm delivery (1.37, 1.33-1.42) and SGA (1.26, 1.19-1.33), but not preeclampsia (0.99, 0.93-1.05). Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia.
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http://dx.doi.org/10.1093/aje/kwab132DOI Listing
June 2021

Stress levels among an international sample of pregnant and postpartum women during the COVID-19 pandemic.

J Matern Fetal Neonatal Med 2021 Jun 22:1-9. Epub 2021 Jun 22.

Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Stress is a complex condition that can have a profound effect on an individual's sense of wellbeing and their ability to live a happy and healthy life. COVID-19 and its associated stressors have the potential to disrupt numerous facets of our everyday lives. Pregnant and postpartum women are especially vulnerable to changes in the availability of routine health and social care services and of their support networks. The current study sought to explore stress levels and their influencers among an international cohort of pregnant and postpartum women during the COVID-19 pandemic.

Methods: We conducted an anonymous, online, cross-sectional survey in 64 countries between May and June 2020. The survey was hosted on the Pregistry platform and made available in 12 languages, with respondents sought through a variety of social media platforms and parenting forums. In addition to levels of stress, we collected data related to demographics, COVID-19 exposure and worries, lifestyle changes, traditional and social media use, precautionary measures related to COVID-19, and mental health.

Results: In total, 7185 women were included in our sample. We found statistically significant (-value <0.05) reductions in stress score among older women (≥35 years of age), those either living with a partner or married, those who had graduated from college, and those with medical coverage. Higher stress scores were found among women who resided in Africa, Asia and the Pacific, the Middle East, and North America compared with those in Europe. When race and ethnicity were included in the model, black women were found to have higher stress compared to white women. Level of family and community support was inversely associated with level of stress.

Conclusion: Our study is one of the first to explore stress levels among pregnant and postpartum women during the COVID-19 pandemic. We found statistically significant differences in stress levels by age, education, marital status, region of residence, race/ethnicity and level of support. Understanding stress during the COVID-19 pandemic, and exploring ways to address it, will be key to contributing to the mental and physical health of expectant and new mothers, as well as their children, in both the short and long term.
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http://dx.doi.org/10.1080/14767058.2021.1936489DOI Listing
June 2021

Anticonvulsant Primary and Secondary Prophylaxis for Acute Ischemic Stroke Patients: A Decision Analysis.

Stroke 2021 Aug 15;52(9):2782-2791. Epub 2021 Jun 15.

Department of Neurology (F.J.S.J., P.R.S., J.R.S., S.F.Z., L.H.S., M.B.W., L.M.V.R.M.), Massachusetts General Hospital, Boston.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384723PMC
August 2021

A cross-national study of factors associated with women's perinatal mental health and wellbeing during the COVID-19 pandemic.

PLoS One 2021 21;16(4):e0249780. Epub 2021 Apr 21.

Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Pregnant and postpartum women face unique challenges during the COVID-19 pandemic that may put them at elevated risk of mental health problems. However, few large-scale and no cross-national studies have been conducted to date that investigate modifiable pandemic-related behavioral or cognitive factors that may influence mental health in this vulnerable group. This international study sought to identify and measure the associations between pandemic-related information seeking, worries, and prevention behaviors on perinatal mental health during the COVID-19 pandemic. An anonymous, online, cross-sectional survey of pregnant and postpartum women was conducted in 64 countries between May 26, 2020 and June 13, 2020. The survey, available in twelve languages, was hosted on the Pregistry platform for COVID-19 studies (https://corona.pregistry.com) and advertised in social media channels and online parenting forums. Participants completed measures on demographics, COVID-19 exposure and worries, information seeking, COVID-19 prevention behaviors, and mental health symptoms including posttraumatic stress via the IES-6, anxiety/depression via the PHQ-4, and loneliness via the UCLA-3. Of the 6,894 participants, substantial proportions of women scored at or above the cut-offs for elevated posttraumatic stress (2,979 [43%]), anxiety/depression (2,138 [31%], and loneliness (3,691 [53%]). Information seeking from any source (e.g., social media, news, talking to others) five or more times per day was associated with more than twice the odds of elevated posttraumatic stress and anxiety/depression, in adjusted models. A majority of women (86%) reported being somewhat or very worried about COVID-19. The most commonly reported worries were related to pregnancy and delivery, including family being unable to visit after delivery (59%), the baby contracting COVID-19 (59%), lack of a support person during delivery (55%), and COVID-19 causing changes to the delivery plan (41%). Greater worries related to children (i.e., inadequate childcare, their infection risk) and missing medical appointments were associated with significantly higher odds of posttraumatic stress, anxiety/depression and loneliness. Engaging in hygiene-related COVID-19 prevention behaviors (face mask-wearing, washing hands, disinfecting surfaces) were not related to mental health symptoms or loneliness. Elevated posttraumatic stress, anxiety/depression, and loneliness are highly prevalent in pregnant and postpartum women across 64 countries during the COVID-19 pandemic. Excessive information seeking and worries related to children and medical care are associated with elevated symptoms, whereas engaging in hygiene-related preventive measures were not. In addition to screening and monitoring mental health symptoms, addressing excessive information seeking and women's worries about access to medical care and their children's well-being, and developing strategies to target loneliness (e.g., online support groups) should be part of intervention efforts for perinatal women. Public health campaigns and medical care systems need to explicitly address the impact of COVID-19 related stressors on mental health in perinatal women, as prevention of viral exposure itself does not mitigate the pandemic's mental health impact.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249780PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059819PMC
May 2021

Safety of Tenofovir Disoproxil Fumarate (TDF) for Pregnant Women facing the COVID-19 Pandemic.

Am J Epidemiol 2021 Apr 13. Epub 2021 Apr 13.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic Extract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled ≥1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by ICD-9 codes using validated algorithms. Relative risks (RR) and 95% confidence intervals (CI) were estimated using propensity score (PS) stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted RR was 1.21 (95% CI 0.77 to 1.90). Estimates for specific malformations were imprecise. The pooled RR from the meta-analysis with six prior studies was 0.88 (0.75 to 1.03). Based on evidence accumulated in patients with HIV, first trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared to other ART.
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http://dx.doi.org/10.1093/aje/kwab109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083317PMC
April 2021

The Patterns of Use of Medications for Inflammatory Bowel Disease During Pregnancy in the US and Sweden Are Changing.

Inflamm Bowel Dis 2021 Aug;27(9):1427-1434

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Population-level data spanning different countries describing oral and parenteral treatment in pregnant women with inflammatory bowel disease (IBD) are scarce. We studied treatment with sulfasalazine/5-aminosalicylates, corticosteroids, thiopurines/immunomodulators, and tumor necrosis factor (TNF)-inhibitors in the United States (Optum Clinformatics Data Mart and the Medicaid Analytics Extract [MAX]) and in the Swedish national health registers.

Methods: We identified 2975 pregnant women in Optum (2004-2013), 3219 women in MAX (2001-2013), and 1713 women in Sweden (2006-2015) with a recorded diagnosis of IBD. We assessed patterns of use for each drug class according to filled prescriptions, assessing frequency of treatment continuation in those that were treated in the prepregnancy period.

Results: The proportion of women with Crohn's disease and ulcerative colitis on any treatment during pregnancy was 56.1% and 56.3% in Optum, 47.5% and 49.3% in MAX, and 61.3% and 64.7% in Sweden, respectively, and remained stable over time. Sulfasalazine/5-aminosalicylates was the most commonly used treatment in Crohn's disease, ranging from 25.1% in MAX to 31.8% in Optum, and in ulcerative colitis, ranging from 34.9% in MAX to 53.6% in Sweden. From 2006 to 2012, the TNF-inhibitor use increased from 5.0% to 15.5% in Optum, from 3.6% to 8.5% in MAX, and from 0.7% to 8.3% in Sweden. Continuing TNF-inhibitor treatment throughout pregnancy was more common in Optum (55.8%) and in MAX (43.0%) than in Sweden (11.8%).

Conclusions: In this population-based study from 2 countries, the proportion of women with IBD treatment in pregnancy remained relatively constant. TNF-inhibitor use increased substantially in both countries.
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http://dx.doi.org/10.1093/ibd/izaa294DOI Listing
August 2021

The safety of asthma medications during pregnancy and lactation: Clinical management and research priorities.

J Allergy Clin Immunol 2021 06 10;147(6):2009-2020. Epub 2021 Mar 10.

Kaiser Permanente Medical Center, San Diego, Calif.

Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner.
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http://dx.doi.org/10.1016/j.jaci.2021.02.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185876PMC
June 2021

Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Arch Womens Ment Health 2021 08 12;24(4):659-667. Epub 2021 Mar 12.

Ammon-Pinizzotto Center for Women's Mental Health, Massachusetts General Hospital, Boston, MA, USA.

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18-45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765.
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http://dx.doi.org/10.1007/s00737-021-01115-6DOI Listing
August 2021

Tetanus, Diphtheria, Acellular Pertussis Vaccination During Pregnancy and Risk of Pertussis in the Newborn in Publicly and Privately Insured Mother-infant Pairs in the United States.

Pediatr Infect Dis J 2021 Jul;40(7):681-687

From the Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: In the United States, pertussis circulation persists and primarily infects infants and children, despite routine vaccinations. To minimize infant morbidity and mortality from the disease before the first DTaP dose, the Advisory Committee on Immunization Practices recommends maternal Tdap vaccination in weeks 27-36 of pregnancy.

Methods: Cohorts of mother-infant pairs in the Medicaid Analytic eXtract (MAX) (2010-2014) and IBM MarketScan (2011-2015) databases were analyzed to estimate the effectiveness of prenatal Tdap vaccination compared with no vaccination to prevent infant pertussis in the first 6 months. Hazard ratios were estimated with Cox proportional hazards models and adjusted for potential confounders via inverse probability weights. The impact of preterm delivery on the risk of pertussis was analyzed. Results from the 2 databases were pooled.

Results: In MarketScan, women received Tdap vaccination before delivery in 114,067 (25.6%) of 445,638 pregnancies and in MAX, 33,286 (4.8%) of 695,262 pregnancies. Among pregnancies with preterm delivery, only 21.2% and 3.8% in MarketScan and MAX had been vaccinated. The risk of pertussis in unvaccinated term infants was 3.5 (MarketScan) and 17 (MAX) per 10,000; and in preterm infants, it was 8.4 (MarketScan) and 19.8 (MAX) per 10,000. The pooled hazard ratio for Tdap vaccination any time before delivery versus no vaccination was 0.64 [95% confidence interval (CI): 0.41-1.00]. The hazard ratio was 0.11 (95% CI: 0.03-0.36) for preterm and 0.78 (95% CI: 0.48-1.29) for term infants vaccinated before 37 weeks. The incidence of pertussis was higher and the protective hazard ratio stronger during pertussis outbreaks.

Conclusions: Prenatal Tdap vaccination reduces the risk of pertussis infections in the infants' first 6 months by 36%. Vaccination soon after 27 weeks of pregnancy, before when deliveries began, ensures vaccination includes those born preterm, who are at highest risk for pertussis and benefit particularly from this vaccination.
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http://dx.doi.org/10.1097/INF.0000000000003099DOI Listing
July 2021

COVID-19 vaccine acceptance among pregnant women and mothers of young children: results of a survey in 16 countries.

Eur J Epidemiol 2021 Feb 1;36(2):197-211. Epub 2021 Mar 1.

Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

With the development of multiple effective vaccines, reducing the global morbidity and mortality of COVID-19 will depend on the distribution and acceptance of COVID-19 vaccination. Estimates of global vaccine acceptance among pregnant women and mothers of young children are yet unknown. An understanding of the challenges and correlates to vaccine acceptance will aid the acceleration of vaccine administration within these populations. Acceptance of COVID-19 vaccination among pregnant women and mothers of children younger than 18-years-old, as well as potential predictors, were assessed through an online survey, administered by Pregistry between October 28 and November 18, 2020. 17,871 total survey responses from 16 countries were obtained. Given a 90% COVID-19 vaccine efficacy, 52.0% of pregnant women (n = 2747/5282) and 73.4% of non-pregnant women (n = 9214/12,562) indicated an intention to receive the vaccine. 69.2% of women (n = 11,800/17,054), both pregnant and non-pregnant, indicated an intention to vaccinate their children. Vaccine acceptance was generally highest in India, the Philippines, and all sampled countries in Latin America; it was lowest in Russia, the United States and Australia. The strongest predictors of vaccine acceptance included confidence in vaccine safety or effectiveness, worrying about COVID-19, belief in the importance of vaccines to their own country, compliance to mask guidelines, trust of public health agencies/health science, as well as attitudes towards routine vaccines. COVID-19 vaccine acceptance and its predictors among women vary globally. Vaccination campaigns for women and children should be specific for each country in order to attain the largest impact.
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http://dx.doi.org/10.1007/s10654-021-00728-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920402PMC
February 2021

Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study.

BMJ 2021 02 10;372:n102. Epub 2021 Feb 10.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA.

Objective: To evaluate the risk of first trimester exposure to prescription opioids for major congenital malformations, previously reported to be associated with such exposure.

Design: Population based cohort study.

Setting: Nationwide sample of publicly and commercially insured pregnant women linked to their liveborn infants, nested in the Medicaid Analytic eXtract (MAX, 2000-14) and the MarketScan Research Database (MarketScan, 2003-15).

Participants: 1 602 580 publicly insured (MAX) and 1 177 676 commercially insured (MarketScan) pregnant women with eligibility from at least three months before pregnancy to one month after delivery; infants with eligibility for at least three months after birth.

Interventions: Use of prescription opioids was ascertained by requiring two or more dispensations of any opioid during the first trimester.

Main Outcomes Measures: Major malformations overall, cardiac malformations overall, ventricular septal defect, secundum atrial septal defect/patent foramen ovale, neural tube defect, clubfoot, and oral cleft, defined based on validated algorithms. Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders. Estimates from each database were combined using meta-analysis.

Results: 70 447 (4.4%) of 1 602 580 publicly insured and 12 454 (1.1%) of 1 177 676 commercially insured pregnant women had two or more dispensations of an opioid during the first trimester. Absolute risk of malformations overall was 41.0 (95% confidence interval 39.5 to 42.5) per 1000 pregnancies exposed to opioids versus 32.0 (31.7 to 32.3) per 1000 unexposed pregnancies in the MAX cohort, and 42.6 (39.0 to 46.1) and 37.3 (37.0 to 37.7) per 1000, respectively, in the MarketScan cohort. Pooled unadjusted relative risk estimates were raised for all outcomes but shifted substantially toward the null after adjustment; for malformations overall (relative risk 1.06, 95% confidence interval 1.02 to 1.10), cardiovascular malformations (1.09, 1.00 to 1.18), ventricular septal defect (1.07, 0.95 to 1.21), atrial septal defect/patent foramen ovale (1.04, 0.88 to 1.24), neural tube defect (0.82, 0.53 to 1.27), and clubfoot (1.06, 0.88 to 1.28). The relative risk for oral clefts remained raised after adjustment (1.21, 0.98 to 1.50), with a higher risk of cleft palate (1.62, 1.23 to 2.14).

Conclusions: Prescription opioids used in early pregnancy are not associated with a substantial increase in risk for most of the malformation types considered, although a small increase in the risk of oral clefts associated with their use is possible.
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http://dx.doi.org/10.1136/bmj.n102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873721PMC
February 2021

Hydroxychloroquine early in pregnancy and risk of birth defects: absence of evidence is not the same as evidence of absence.

Am J Obstet Gynecol 2021 05 9;224(5):549-550. Epub 2021 Jan 9.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

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http://dx.doi.org/10.1016/j.ajog.2020.12.1219DOI Listing
May 2021

Chronic prescription opioid use in pregnancy in the United States.

Pharmacoepidemiol Drug Saf 2021 04 17;30(4):504-513. Epub 2021 Jan 17.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Purpose: To evaluate chronic opioid utilization patterns during pregnancy using nationwide data from publicly and commercially insured women.

Methods: Pregnancy cohorts were identified using data from the Medicaid Analytic eXtract 2008-2014 and the IBM Health MarketScan Research Database 2008-2015. Opioid dispensing was evaluated using claims from filled prescriptions. Two different definitions of chronic opioid use were employed: ≥90 days' supply and ≥180 days' supply of prescription opioids during pregnancy. Patient characteristics were assessed and variations in the prevalence of chronic opioid therapy were described by geographic region and over time.

Results: 1.50% of 975 169 Medicaid-insured and 0.32% of 1 037 599 commercially insured beneficiaries filled opioid prescriptions for ≥90 days' supply; 0.78% (Medicaid) and 0.17% (commercially insured) filled prescriptions for ≥180 days' supply. Prevalence approximately doubled in Medicaid beneficiaries during the study period, while it remained relatively stable for commercial insurance beneficiaries. The most commonly prescribed opioid for chronic therapy was hydrocodone, followed by oxycodone and tramadol. Indications commonly associated with chronic use were back/neck pain, abdominal/pelvic pain, musculoskeletal pain and migraine/headache. Substantial regional variation was observed, with several states reporting a frequency of ≥90 days' supply in excess of 3% in Medicaid-insured patients.

Conclusions: Despite growing awareness of the risks associated with chronic opioid use and emphasis on improving opioid prescription patterns, prevalence of chronic use in pregnancy among publicly insured women nearly doubled from 2008-2014 and was 5-fold more common when compared to commercially insured women. Findings call for the development of guidelines on chronic pain management during pregnancy.
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http://dx.doi.org/10.1002/pds.5194DOI Listing
April 2021

Antiemetic Drugs During Pregnancy: What Can We Learn From Spontaneous Reporting System Database Analyses?-Reply.

JAMA Pediatr 2021 Mar;175(3):327-328

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamapediatrics.2020.5177DOI Listing
March 2021

Active Surveillance of the Safety of Medications Used During Pregnancy.

Am J Epidemiol 2021 06;190(6):1159-1168

The scientific community relies on postmarketing approaches to define the risk of using medications in pregnancy because information available at the time of drug approval is limited. Most studies carried out in pregnancy focus on a single outcome or selected outcomes. However, women must balance the benefit of treatment against all possible adverse effects. We aimed to apply and evaluate a tree-based scan statistic data-mining method (TreeScan; Martin Kulldorff, Harvard Medical School, Boston, Massachusetts) as a safety surveillance approach that allows for simultaneous evaluation of a comprehensive range of adverse pregnancy outcomes, while preserving the overall rate of false-positive alerts. We evaluated TreeScan with a cohort design and adjustment via propensity score techniques, using 2 test cases: 1) opioids and neonatal opioid withdrawal syndrome and 2) valproate and congenital malformations, implemented in pregnancy cohorts nested within the Medicaid Analytic eXtract (January 1, 2000-December 31, 2014) and the IBM MarketScan Research Database (IBM, Armonk, New York) (January 1, 2003-September 30, 2015). In both cases, we identified known safety concerns, with only 1 previously unreported alert at the preset statistical alerting threshold. This evaluation shows the promise of TreeScan-based approaches for systematic drug safety monitoring in pregnancy. A targeted screening approach followed by deeper investigation to refine understanding of potential signals will ensure that pregnant women and their physicians have access to the best available evidence to inform treatment decisions.
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http://dx.doi.org/10.1093/aje/kwaa288DOI Listing
June 2021

Prescription opioid use after vaginal delivery and subsequent persistent opioid use and misuse.

Am J Obstet Gynecol MFM 2021 03 28;3(2):100304. Epub 2020 Dec 28.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.

Background: Vaginal delivery is the most common reason for hospitalization in the United States, and approximately 30% of women fill an opioid prescription after vaginal delivery, making this a common source of opioid exposure in women of reproductive age.

Objective: This study aimed to evaluate the effect of receiving an opioid prescription after vaginal delivery on the risk of subsequent persistent opioid use, opioid use disorders, and overdose.

Study Design: We assembled a nationwide cohort of Medicaid beneficiaries in the United States using the Medicaid Analytic eXtract 2009-2014. The study population included pregnant women who delivered vaginally between 2009 and 2013 and were continuously enrolled in Medicaid from 90 days before to 365 days after delivery. We identified patients with prescription opioids dispensed within 7 days of the date of vaginal delivery. Persistent opioid use was defined as ≥10 opioid fills or >120 days' supply dispensed from 30 to 365 days after delivery. Incident diagnoses of opioid use disorder and overdose were ascertained during the same interval. Propensity score matching was used to control for potential confounding factors.

Results: Among 459,829 pregnancies ending in vaginal deliveries, 140,807 (30.62%) had an opioid dispensed within 7 days of delivery. Overall, 5770 of 140,807 (4.10%) women who filled an opioid prescription vs 2668 of 319,022 (0.84%) unexposed women had subsequent persistent opioid use, with an unadjusted relative risk of 4.90 (95% confidence interval, 4.68-5.13) and a risk difference of 3.26% (95% confidence interval, 3.15-3.37). After propensity score matching, the risk remained higher among pregnancies with an opioid prescription dispensed, with a relative risk of 2.57 (95% confidence interval, 2.43-2.72) and a risk difference of 2.21% (95% confidence interval, 2.08-2.33), which was confirmed by the instrumental variable analysis with a risk difference of 1.31% (95% confidence interval, 1.06-1.56) by using the rate of opioid prescribing at the delivery facility in a given geographic region as the instrument. The adjusted relative risk of newly diagnosed opioid use disorder and overdose was 1.48 (95% confidence interval, 1.40-1.57) and 1.92 (95% confidence interval, 1.20-3.09), respectively.

Conclusion: Opioid dispensing following vaginal delivery is associated with future persistent opioid use and misuse, independent of confounding factors. Opioid prescriptions to women after vaginal delivery should be avoided, except in rare circumstances.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100304DOI Listing
March 2021

Polypharmacy and comorbidities during pregnancy in a cohort of women with migraine.

Cephalalgia 2021 03 3;41(3):392-403. Epub 2020 Dec 3.

Department of Epidemiology, T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

Objective: To describe longitudinal patterns of medication use throughout pregnancy in women with migraine.

Methods: We used the IBM MarketScan healthcare claims database in the US to create a cohort of pregnancies enrolled between 2011-2015 resulting in live or stillbirth. Migraine headache was identified based on ICD-9-CM diagnosis codes or procedure codes recorded in clinical encounters. Outcomes were patterns of prescriptions filled for medications that may be used to prevent migraine (antiepileptics, antihypertensives, antidepressants) or treat acute episodes (opioids, triptans, acetaminophen) and of other comorbid conditions (hypertension, psychiatric diagnoses, epilepsy). We used group-based multi-trajectory models to cluster women into similar longitudinal patterns of prescription fills.

Results: Of 859,501 pregnancies, 8168 had migraine. Within migraineurs, before pregnancy, the most commonly filled prescription was for a triptan (43.2%), followed by opioids (26.7%), acetaminophen (26.2%), antidepressants (24.9%), antiepileptics (18.6%) and antihypertensives (12.3%). Antiepileptics, antidepressants, and triptans were frequently discontinued early in pregnancy with few new users, while antihypertensives were discontinued by some users, but continued or initiated by a minority of users late in pregnancy. Opioids and acetaminophen were used intermittently throughout pregnancy. Comorbidities included hypertension (10.8%), epilepsy (4.7%), depression (14.0%), and anxiety (15.6%). Polypharmacy involving both preventive and acute medications was most common before pregnancy (31.4%) and declined in first trimester (14.7%). In all, 25.9% of women filled prescriptions for two or more acute medications before pregnancy.

Conclusions: Medication use patterns during pregnancy for women with migraine are complex. Patterns of polypharmacy and comorbidity during pregnancy highlight an under-studied area relevant for maternal and child health outcomes.
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http://dx.doi.org/10.1177/0333102420975394DOI Listing
March 2021

Development and Validation of a Pediatric Comorbidity Index.

Am J Epidemiol 2021 05;190(5):918-927

Comorbidity scores are widely used to help address confounding bias in nonrandomized studies conducted within health-care databases, but existing scores were developed to predict all-cause mortality in adults and might not be appropriate for use in pediatric studies. We developed and validated a pediatric comorbidity index, using health-care utilization data from the tenth revision of the International Classification of Diseases. Within the MarketScan database of US commercial claims data, pediatric patients (aged ≤18 years) continuously enrolled between October 1, 2015, and September 30, 2017, were identified. Logistic regression was used to predict the 1-year risk of hospitalization based on 27 predefined conditions and empirically identified conditions derived from the most prevalent diagnoses among patients with the outcome. A single numerical index was created by assigning weights to each condition based on its β coefficient. We conducted internal validation of the index and compared its performance with existing adult scores. The pediatric comorbidity index consisted of 24 conditions and achieved a C statistic of 0.718 (95% confidence interval (CI): 0.714, 0.723). The index outperformed existing adult scores in a pediatric population (C statistics ranging from 0.522 to 0.640). The pediatric comorbidity index provides a summary measure of disease burden and can be used for risk adjustment in epidemiologic studies of pediatric patients.
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http://dx.doi.org/10.1093/aje/kwaa244DOI Listing
May 2021

Antidiabetic medication use in commercially insured children and adolescents in the United States from 2004 to 2019.

Diabetes Obes Metab 2021 02 18;23(2):444-454. Epub 2020 Nov 18.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.

Aim: To describe the patterns of non-insulin antidiabetic medication use, initiation and adherence in the paediatric population.

Methods: We conducted a descriptive study of non-insulin antidiabetic medication use in children and adolescents (aged 10-18 years) using real-world data from a nationwide US commercial claims database (January 2004-September 2019). Trends in the prevalence of non-insulin antidiabetic medication use overall and by class were evaluated. Among new users of non-insulin antidiabetic agents, medication adherence was examined using group-based trajectory models.

Results: In a cohort of more than 1 million paediatric patients, the prevalence of any non-insulin antidiabetic medication use was 75.7 per 100 000 patients in 2004 and more than doubled to 162.0 per 100 000 in 2019. Biguanides (metformin) was by far the most widely used medication class. The use of newer classes was low (<10 per 100 000), but there was an uptake in the use of glucagon-like peptide-1 receptor agonists after liraglutide received paediatric approval in 2019. Medication adherence was poor during the 18 months after treatment initiation: 79.6% of initiators experienced an early treatment interruption (median time to interruption: 90 days among metformin monotherapy initiators) and 21% of initiators did not return for a prescription refill after the first month.

Conclusions: There was a substantial increase in non-insulin antidiabetic medication use among commercially insured paediatric patients from 2004 to 2019. Nearly all patients were treated with metformin, while the use of newer agents remained low. Despite the increase in medication use, short treatment episodes were observed, even among patients with a diagnosis of type 2 diabetes, raising concern over poor adherence.
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http://dx.doi.org/10.1111/dom.14237DOI Listing
February 2021

Predicting overdose among individuals prescribed opioids using routinely collected healthcare utilization data.

PLoS One 2020 20;15(10):e0241083. Epub 2020 Oct 20.

Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.

Introduction: With increasing rates of opioid overdoses in the US, a surveillance tool to identify high-risk patients may help facilitate early intervention.

Objective: To develop an algorithm to predict overdose using routinely-collected healthcare databases.

Methods: Within a US commercial claims database (2011-2015), patients with ≥1 opioid prescription were identified. Patients were randomly allocated into the training (50%), validation (25%), or test set (25%). For each month of follow-up, pooled logistic regression was used to predict the odds of incident overdose in the next month based on patient history from the preceding 3-6 months (time-updated), using elastic net for variable selection. As secondary analyses, we explored whether using simpler models (few predictors, baseline only) or different analytic methods (random forest, traditional regression) influenced performance.

Results: We identified 5,293,880 individuals prescribed opioids; 2,682 patients (0.05%) had an overdose during follow-up (mean: 17.1 months). On average, patients who overdosed were younger and had more diagnoses and prescriptions. The elastic net model achieved good performance (c-statistic 0.887, 95% CI 0.872-0.902; sensitivity 80.2, specificity 80.1, PPV 0.21, NPV 99.9 at optimal cutpoint). It outperformed simpler models based on few predictors (c-statistic 0.825, 95% CI 0.808-0.843) and baseline predictors only (c-statistic 0.806, 95% CI 0.787-0.26). Different analytic techniques did not substantially influence performance. In the final algorithm based on elastic net, the strongest predictors were age 18-25 years (OR: 2.21), prior suicide attempt (OR: 3.68), opioid dependence (OR: 3.14).

Conclusions: We demonstrate that sophisticated algorithms using healthcare databases can be predictive of overdose, creating opportunities for active monitoring and early intervention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241083PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575098PMC
December 2020

Patterns of anticonvulsant use and adverse drug events in older adults.

Pharmacoepidemiol Drug Saf 2021 01 2;30(1):28-36. Epub 2020 Oct 2.

Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts.

Purpose: To examine indications for, duration of use, and rate of adverse drug events (ADE) attributable to anticonvulsant initiation, as adjudicated by expert review of electronic health records (EHR) of older adults.

Methods: We identified a cohort of community dwelling Medicare beneficiaries with linked EHR (aged 65+, continuously enrolled with a large health system/until death between 2012 and 2014, n = 20 945) and drew a stratified EHR review sample (n = 1534). An expert reviewed all records to adjudicate anticonvulsant use, years of use, indication for use, and evidence of ADEs attributable to anticonvulsant initiation. After excluding patients with insufficient EHR data (n = 37; 2%), we reconstructed the cohort using inverse probability weights to resemble the original cohort of eligible beneficiaries (n = 20 380). Among incident users of a single anticonvulsant, we estimated the rate of ADEs and described the type and severity of ADEs.

Results: Overall, 12% (n = 2469) of eligible beneficiaries used at least one anticonvulsant in the 2012 to 2014 period (4% [n = 757] incident users, 8% [n = 1712] prevalent users). Incident users were most frequently prescribed gabapentin (n = 461/757, 61%), benzodiazepines (n = 122/757, 16%), and levetiracetam (n = 74/757, 10%); the most common indication was pain relief (n = 214; 28%) followed by epilepsy (n = 53; 7%). Among incident users, the overall ADE rate was 10/100 person-years (95% CI 4-20/100 person-years), of which 29% (n = 28/97) were life threatening (eg, somnolence). Most ADEs among incident monotherapy users were nervous system related (68%, n = 66/97).

Conclusion: Many older adult community dwelling traditional Medicare beneficiaries had clinically significant ADEs likely attributable to the initiation of anticonvulsant therapy, which was begun for a range of indications.
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http://dx.doi.org/10.1002/pds.5139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849867PMC
January 2021

Hydroxychloroquine early in pregnancy and risk of birth defects.

Am J Obstet Gynecol 2021 03 19;224(3):290.e1-290.e22. Epub 2020 Sep 19.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.

Background: Hydroxychloroquine is generally considered safe in pregnancy for the treatment of rheumatic conditions, but studies have been too small to evaluate teratogenicity. Quantifying the risk of congenital malformations associated with early pregnancy exposure to hydroxychloroquine is important in both the context of its ongoing use for rheumatological disorders and its potential future use for coronavirus disease 2019 prophylaxis, for which a number of clinical trials are ongoing despite initial trials for coronavirus disease 2019 treatment having been negative.

Objective: The study objective was to evaluate the risk of major congenital malformations associated with exposure to hydroxychloroquine during the first trimester of pregnancy, the period of organogenesis.

Study Design: We performed a population-based cohort study nested in the Medicaid Analytic eXtract (MAX, 2000-2014) and IBM MarketScan Research Database (MarketScan, 2003-2015). The source cohort included 2045 hydroxychloroquine-exposed pregnancies and 3,198,589 pregnancies not exposed to hydroxychloroquine continuously enrolled in their respective insurance program for 3 months before the last menstrual period through at least 1 month after delivery; infants were enrolled for at least 3 months after birth. We compared the risk of congenital malformations in women using hydroxychloroquine during the first trimester of pregnancy with that of those not using hydroxychloroquine, restricting the cohort to women with rheumatic disorders and using propensity score matching to control for indication, demographics, medical comorbidities, and concomitant medications (1867 hydroxychloroquine-exposed pregnancies and 19,080 pregnancies not exposed to hydroxychloroquine). The outcomes considered included major congenital malformations diagnosed during the first 90 days after delivery and specific malformation types for which there were at least 5 exposed events: oral cleft, cardiac, respiratory, gastrointestinal, genital, urinary, musculoskeletal, and limb defects.

Results: Overall, 54.8 per 1000 infants exposed to hydroxychloroquine were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Patient characteristics were balanced in the restricted, propensity score-matched cohort. The adjusted relative risk was 1.26 (95% confidence interval, 1.04-1.54); it was 1.33 (95% confidence interval, 1.08-1.65) for a daily dose of ≥400 mg and 0.95 (95% confidence interval, 0.60-1.50) for a daily dose of <400 mg. Among the different malformation groups considered, more substantial increases in the risk of oral clefts, respiratory anomalies, and urinary defects were observed, although estimates were imprecise. No pattern of malformation was identified.

Conclusion: Our findings suggest a small increase in the risk of malformations associated with first-trimester hydroxychloroquine use. For most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy will likely outweigh this risk. If hydroxychloroquine were shown to be effective for coronavirus disease 2019 prophylaxis in ongoing trials, the risk of malformations would need to be balanced against such benefits.
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http://dx.doi.org/10.1016/j.ajog.2020.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501839PMC
March 2021

Trends in Human Papillomavirus Vaccination in Commercially Insured Children in the United States.

Pediatrics 2020 10 14;146(4). Epub 2020 Sep 14.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts; and.

Objectives: The human papillomavirus (HPV) vaccine was recommended in 2006 for girls and in 2011 for boys. The Healthy People 2020 goal for 2-dose HPV vaccination coverage is 80% by age 15 for girls and boys. We used nationwide population-based data to describe trends in HPV vaccination in children.

Methods: We conducted a cohort study nested within the MarketScan health care database between January 2003 and December 2017. Children were followed from the year they turned 9 until HPV vaccination, insurance disenrollment, or the end of the year when they turned 17, whichever came first. We estimated the cumulative incidence of at least 1- and 2-dose HPV vaccination, stratified by birth year, sex, and state. In secondary analyses, we evaluated the association between state-level vaccination policies and HPV vaccination coverage.

Results: This study included 7 837 480 children and 19.8 million person-years. The proportion of 15-year-old girls and boys with at least a 1-dose HPV vaccination increased from 38% and 5% in 2011 to 57% and 51% in 2017, respectively; the proportion with at least a 2-dose vaccination went from 30% and 2% in 2011 to 46% and 39% in 2017, respectively. By 2017, 2-dose HPV vaccination coverage varied from 80% in Washington, District of Columbia, among girls to 15% in Mississippi among boys and was positively correlated with legislation for HPV vaccine education and pediatrician availability.

Conclusions: Despite the increasing trends in uptake, HPV vaccine coverage among commercially insured children in the United States remains behind target levels, with substantial disparities by state.
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http://dx.doi.org/10.1542/peds.2019-3557DOI Listing
October 2020
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