Women Of Reproductive Potential Research Articles

Dyslipidemia management in women of reproductive potential: An expert clinical consensus from the national lipid association.

Cardiovascular disease (CVD) is the leading cause of death among women and its incidence has been increasing recently, particularly among younger women. Across major professional society guidelines, dyslipidemia management remains a central tenet for atherosclerotic CVD prevention for both women and men. Despite this, women, particularly young women, who are candidates for statin therapy are less likely to be treated and less likely to achieve their recommended therapeutic objectives for low-density lipoprotein cholesterol (LDL-C) levels. Elevated LDL-C and triglycerides are the two most common dyslipidemias that should be addressed during pregnancy due to the increased risk for adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, and pre-term delivery, as well as pancreatitis in the presence of severe hypertriglyceridemia. In this National Lipid Association Expert Clinical Consensus, we review the roles of nutrition, physical activity, and pharmacotherapy as strategies to address elevated levels of LDL-C and/or triglycerides among women of reproductive age. We include a special focus on points to consider during the shared decision-making discussion regarding pharmacotherapy for dyslipidemia during preconception planning, pregnancy, and lactation.

Adverse perinatal outcomes associated with prenatal exposure to protease-inhibitor-based versus non-nucleoside reverse transcriptase inhibitor-based antiretroviral combinations in pregnant women with HIV infection: a systematic review and meta-analysis

BackgroundAbout 1.3 million pregnant women lived with HIV and were eligible to receive antiretroviral therapy (ART) worldwide in 2021. The World Health Organization recommends protease inhibitors (PI)-based regimen as second or third-line during pregnancy. With remaining pregnant women exposed to PIs, there is still an interest to assess whether this treatment affects perinatal outcomes. Adverse perinatal outcomes after prenatal exposure to PI-based ART remain conflicting: some studies report an increased risk of preterm birth (PTB) and low-birth-weight (LBW), while others do not find these results. We assessed adverse perinatal outcomes associated with prenatal exposure to PI-based compared with non-nucleoside reverse transcriptase (NNRTI)-based ART.MethodsWe performed a systematic review searching PubMed, Reprotox, Clinical Trial Registry (clinicaltrials.gov) and abstracts of HIV conferences between 01/01/2002 and 29/10/2021. We used Oxford and Newcastle-Ottawa scales to assess the methodological quality. Studied perinatal outcomes were spontaneous abortion, stillbirth, congenital abnormalities, PTB (< 37 weeks of gestation), very preterm birth (VPTB, < 32 weeks of gestation), LBW (< 2500 grs), very low-birth-weight (VLBW, < 1500 g), small for gestational age (SGA) and very small for gestational age (VSGA). The association between prenatal exposure to PI-based compared to NNRTI-based ART was measured for each adverse perinatal outcome using random-effect meta-analysis to estimate pooled relative risks (RR) and their corresponding 95% confidence intervals (CI). Pre-specified analyses were stratified according to country income and study quality assessment, and summarized when homogeneous.ResultsOut of the 49,171 citations identified, our systematic review included 32 published studies, assessing 45,427 pregnant women. There was no significant association between prenatal exposure to PIs compared to NNRTIs for VPTB, LBW, SGA, stillbirth, and congenital abnormalities. However, it was inconclusive for PTB, and PI-based ART is significantly associated with an increased risk of VSGA (sRR 1.41 [1.08-1.84]; I2 = 0%) compared to NNRTIs.ConclusionsWe did not report any significant association between prenatal exposure to PIs vs NNRTIs-based regimens for most of the adverse perinatal outcomes, except for VSGA significantly increased (+ 41%). The evaluation of antiretroviral exposure on pregnancy outcomes remains crucial to fully assess the benefice-risk balance, when prescribing ART in women of reproductive potential with HIV.PROSPERO numberCRD42022306896.

Prescribing Guideline for Valproic Acid and Women of Reproductive Potential: Forget It Exists.

Prescribing Guideline for Valproic Acid and Women of Reproductive Potential: Forget It Exists.

Assessment of the Association of Periodontal Diseases in Pregnant Women and the Efficacy of Periodontal Treatment in the Context of Premature Births and Pregnancy Complications - a Narrative Review.

Introduction Periodontal diseases are widespread in women of reproductive potential. Although their treatment of these disorders contributes to oral health, there is still no conclusive evidence that this intervention has a beneficial effect on the course of pregnancy, in particular the rate of premature births. On the one hand, the aim of the paper is a systematic assessment of the association between periodontal diseases and pregnancy complications, based on the current literature. On the other hand, the efficacy of periodontal treatments vs. no treatment in pregnant women should be assessed with the target criterion of premature birth or other pregnancy complications. Materials and methods The narrative review was based on the PRISMA statement. Premature births were defined as primary endpoints, while various perinatal and maternal outcomes were grouped together as secondary endpoints. An electronic database search for relevant meta-analyses and systematic reviews was carried out in PubMed and the Cochrane database. Methodological characteristics and the results of the included studies were extracted. The RR or OR (95% CI) was used to measure the result. The quality of the included studies was assessed according to the AMSTAR checklist. Results Seven publications were included (total number of subjects n = 56755). The majority of included studies do not demonstrate a significant association of periodontal disease and/or periodontal treatment with certain childhood and/or maternal outcomes. The quality of the included studies was deemed to be sufficient. Conclusion Even today, there is insufficient evidence to confirm the correlation between periodontal disease and certain maternal and/or infantile outcomes. Periodontal treatment during pregnancy also does not seem to affect the risks of pregnancy. Nevertheless, it is recommended that all pregnant women are advised to improve their daily oral hygiene in order to prevent inflammatory diseases, regardless of the progress of the pregnancy.

“It’s only fatness, it doesn’t kill”: a qualitative study on perceptions of weight gain from use of dolutegravir-based regimens in women living with HIV in Uganda

BackgroundDolutegravir (DTG)-based regimens have been recommended by the WHO as the preferred first-line and second-line HIV treatment in all populations. Evidence suggests an association with weight gain, particularly among black women. Our study investigated perceptions of weight gain from DTG-based regimen use on body image and adherence of antiretroviral therapy in women living with HIV (WLHIV) in Uganda.MethodsBetween April and June 2021, we conducted semi-structured interviews involving 25 WLHIV (adolescents, women of reproductive potential and post-menopausal women) and 19 healthcare professionals (clinicians, nurses, ART managers and counsellors) purposively selected from HIV clinics in Kampala. The interviews explored perceptions of body weight and image; experiences and management of weight related side effects associated with DTG; and knowledge and communication of DTG-related risks. Data was analysed thematically in NVivo 12 software.ResultsOur findings indicate WLHIV in Uganda commonly disliked thin body size and aspired to gain moderate to high level body weight to improve their body image, social standing and hide their sero-positive status. Both WLHIV and healthcare professionals widely associated weight gain with DTG use, although it was rarely perceived as an adverse event and was unlikely to be reported or to alter medication adherence. Clinical management and pharmacovigilance of DTG-related weight gain were hampered by the limited knowledge of WLHIV of the health risks of being over-weight and obesity; lack of diagnostic equipment and resources; and limited clinical guidance for managing weight gain and associated cardiovascular and metabolic comorbidities.ConclusionsThe study highlights the significance of large body-size in promoting psychosocial wellbeing in WLHIV in Uganda. Although weight gain is recognized as a side effect of DTG, it may be welcomed by some WLHIV. Healthcare professionals should actively talk about and monitor for weight gain and occurrence of associated comorbidities to facilitate timely interventions. Improved supply of diagnostic equipment and support with sufficient guidance for managing weight gain for healthcare professionals in Uganda are recommended.

885. Pregnancy Outcomes and Pharmacokinetics in Pregnant Women Living with HIV Exposed to Long-Acting Cabotegravir and Rilpivirine in Clinical Trials

BackgroundLimited data exist among women living with HIV who become pregnant while exposed to long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV). We report outcomes in pregnant participants and LA pharmacokinetic (PK) tail data in pregnant women exposed to CAB+RPV with live births. MethodsWomen of reproductive potential exposed to ≥ 1 dose of CAB+RPV (oral/LA) from ViiV-sponsored Phase 2/3/3b clinical treatment studies and the compassionate use program were included in this analysis and pregnancies identified. Per protocol, upon identification of pregnancy, CAB+RPV was discontinued and an alternative regimen initiated, with continued quarterly PK sampling for 52 weeks post last injection during long-term safety follow-up (LTFU). Descriptive characteristics of pregnant women and birth outcomes and available CAB and RPV PK during pregnancy for those with live births are summarized. ResultsAs of March 31, 2021, 26/325 women of reproductive potential (age 18–49 years) became pregnant while exposed to CAB+RPV (5 oral, 21 LA [including 3 following LA discontinuation]). There were 11 live births (1 oral, 10 LA), of which 10 had no reported congenital abnormalities and 1 had reported congenital ptosis, in a pre-term infant with intrauterine growth restriction. There were 9 elective terminations and 6 miscarriages (5 in first 9 weeks of gestation). Ten women exposed to intramuscular CAB+RPV LA became pregnant with subsequent live birth outcomes, including 3 infants conceived during the PK tail in LTFU. All women were virologically suppressed at time of pregnancy identification. In women becoming pregnant on LA dosing, plasma CAB and RPV concentrations during pregnancy were within the range of expected concentrations in non-pregnant women. Two of 10 women with live births exposed to CAB+RPV LA continued LA therapy during pregnancy (compassionate use program participants). ConclusionPregnancy outcomes in women exposed to CAB+RPV at conception are consistent with earlier findings. There was 1 reported congenital anomaly among 11 live births. CAB and RPV PK tail in pregnancy was within the expected range for non-pregnant women. Ongoing monitoring of birth defects within the antiretroviral pregnancy registry and pregnancy surveillance within the treatment program continues.Disclosures Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Mark Baker, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Claudia Meyer, MBChB, MRCP, MSc, FRCPath, DTM&H, GlaxoSmithKline (Employee, Shareholder) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Herta Crauwels, PhD, Janssen (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Ciara Seal, BS, GlaxoSmithKline (Employee, Shareholder) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee)

IMPACT OF APPLICATION SITE AND BODY MASS INDEX ON ADHESION AND TOLERABILITY OF A LEVONORGESTREL/ETHINYL ESTRADIOL TRANSDERMAL CONTRACEPTIVE DELIVERY SYSTEM

To assess the impacts of application site (buttock, abdomen, or upper torso [excluding breast]) and body mass index (BMI) on adhesion and local tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system (TDS; 120 μg/day levonorgestrel, 30 μg/day ethinyl estradiol). The TDS is indicated as a method of contraception for use in women of reproductive potential with a BMI <30 kg/m2 for whom a combined hormonal contraceptive is appropriate.

A retrospective analysis of incident pregnancy in phase 1 and 2a HIV-1 vaccine study participants does not support concern for adverse pregnancy or birth outcomes

BackgroundPregnancies occur during HIV-1 vaccine clinical trials, despite requirements for women of reproductive potential to use effective contraception. Deployment of an effective HIV-1 vaccine regimen will likely target adolescents and young adults and therefore safety for pregnant and breastfeeding women will need to be addressed.MethodsWe performed a retrospective, cross-protocol analysis to identify and compare pregnancy outcomes reported in 53 Phase 1 and Phase 2a HIV-1 vaccine clinical trials conducted by the HIV Vaccine Trials Network (HVTN).ResultsTwo thousand six hundred seventy-three women of reproductive potential were identified and 193 pregnancies were reported. 39 of 53 (74%) studies had at least one pregnancy reported with an overall pregnancy rate of 3.15 per 100 woman-years (w-yr). While active contraception use was required during study participation, 13 of the 53 studies also contained a long-term follow up period during which pregnancy was no longer discouraged. The pregnancy rate during main study participation was 3.09 per 100 w-yr, while pregnancies occurred at a slightly greater rate in the long-term follow up period (3.22 per 100 w-yr). Adverse pregnancy outcomes were reported at similar rates between vaccinees and placebo recipients when vaccine vectors, adjuvant used, or geographic region were examined.ConclusionAlthough there is considerable heterogeneity amongst the different vaccine trials, there appears to be no obvious indication of increased risk of adverse pregnancy or birth outcomes in these early phase HIV-1 vaccine studies. More complete data on pregnancy outcomes should be collected in early phase HIV-1 vaccine clinical trials to better inform subsequent efficacy trials.

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review

(Anesth Analg. 2020;130:1628–1637) The approval in 2008 for clinical use of the drug sugammadex has led to its rapid replacement of neostigmine to reverse rocuronium and vecuronium’s neuromuscular blocking (NMB) effects. While its cost is higher, sugammadex’s effectiveness and relative lack of side effects render it the superior choice compared with neostigmine. However, while thorough studies exist for this medication, few of them apply to its use in pregnancy and for women of childbearing potential. Thus, the author’s aim of this narrative was to review the use of sugammadex in pregnant women undergoing nonobstetric surgery, women potentially capable of childbearing using hormone-based contraception, lactating women, and parturients undergoing cesarean delivery (CD), as well as to provide up-to-date evidence in these cases.

The updated South African National Guideline for the Prevention of Mother to Child Transmission of Communicable Infections (2019).

The updated South African National Guideline for the Prevention of Mother to Child Transmission of Communicable Infections (2019).

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review.

Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients.

Cost-effectiveness analysis of pre-ART HIV drug resistance testing in Kenyan women

BackgroundThe prevalence of pre-treatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitor (NNRTI) agents is increasing in sub-Saharan Africa, which may decrease the effectiveness of efavirenz-based antiretroviral therapy (ART) programs. However, due to recent safety concerns, there has been hesitancy to replace efavirenz-based ART with dolutegravir in women of reproductive potential. Our objective was to evaluate whether PDR testing for women not initiating dolutegravir-based ART would be a cost-effective strategy to address the challenges posed by PDR. MethodsWe developed an HIV drug resistance model that simulates the emergence and transmission of resistance mutations, calibrated to the Kenyan epidemic. We modeled three care strategies for PDR testing among women not initiating dolutegravir-based ART: no PDR testing, PDR testing with a low-cost point mutation assay, known as oligonucleotide ligation assay (OLA), and PDR testing with consensus sequencing. Using a health sector perspective, this model was used to evaluate the health outcomes, lifetime costs, and cost-effectiveness under each strategy over a 15-year time horizon starting in 2019. FindingsOLA and CS PDR testing were projected to have incremental cost-effectiveness ratios (ICER) of $10,741/QALY gained and $134,396/QALY gained, respectively, which are not cost-effective by national income standards. Viral suppression rates among women at 12 months after ART initiation were 87·8%, 89·0%, and 89·3% with no testing, OLA testing, and CS testing, respectively. PDR testing with OLA and CS were associated with a 0.5% and 0.6% reduction in incidence rate compared to no PDR testing. Initial PDR prevalence among women was 13.1% in 2019. By 2034, this prevalence was 17·6%, 17·4%, and 17·3% with no testing, OLA testing, and CS testing, respectively. InterpretationPDR testing for women is unlikely to be cost-effective in Kenya whether one uses a low-cost assay, such as OLA, or consensus sequencing. FundingNational Institutes of Health, Gilead Sciences.

How we manage Philadelphia-negative myeloproliferative neoplasms in pregnancy.

The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100000 with a peak frequency between 50 and 70years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3·2/100000 maternities per year in the UK. The majority of data regarding Philadelphia-negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre-eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta-analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro-thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre-conceptual planning to the post-partum period, women should have access to joint care from an obstetrician with experience of high-risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia-negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy.

886. Pregnancy Outcomes Following Raltegravir Exposure

BackgroundSafety data are needed regarding HIV treatment in women of reproductive potential and during pregnancy. This review is to evaluate pregnancy outcomes following prospective exposures (exposure report prior to knowledge of pregnancy outcome) to raltegravir during pregnancy.MethodsExposures to raltegravir during pregnancy reported cumulatively through March 26, 2019 to the internal safety database at Merck & Co., Inc. were reviewed. This database includes all reports of pregnancy from clinical trials sponsored by the company, spontaneous post-marketing reports, and noninterventional data sources. Prospective pregnancy reports were evaluated to determine rates of spontaneous abortion, stillbirth, and congenital anomalies, including neural tube defects. Data from two ongoing cohorts of pregnant women with HIV-1 infection, not included in the internal safety database, were also reviewed.ResultsA total of 2,508 prospective pregnancy reports with reported outcomes were identified among women exposed to raltegravir: 919 from the internal safety database (Table 1) and 1,589 from the UK/Ireland and French pregnancy cohorts. Among the 2,508 prospective pregnancy exposures, 945 were in the first trimester, of which 757 were within the periconception period (within 28 days of conception). Of the 471 documented first trimester exposures identified in the internal safety database, the rates of spontaneous abortion (6.9%), stillbirth (1%), and congenital anomalies (1.5% per live births) were similar to the rates observed in the background populations of the United States Among outcomes following any exposure, the rate of congenital anomalies was 3.4% per live births. There were no reports of neural tube defects identified within the internal safety database or among the cohort data.ConclusionProspectively collected pregnancy outcome data do not suggest an association between raltegravir exposure and spontaneous abortion, stillbirth, or congenital anomalies, including neural tube defects. These data support the current HIV treatment recommendations for the use of raltegravir 400 mg twice daily in women of reproductive potential and during pregnancy. Disclosures All Authors: No reported Disclosures.

Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects.

IntroductionThe unexpected identification of a neural tube defect (NTD) safety signal with preconception dolutegravir (DTG) exposure in the Botswana Tsepamo birth outcomes study brought into sharp focus the need for reliable data on use of new antiretrovirals in pregnancy, improved pharmacovigilance systems to evaluate safety of new drugs being introduced into populations including women of reproductive potential, and balanced risk‐benefit messaging when a safety signal is identified.DiscussionThe Tsepamo study NTD safety signal and accompanying regulatory responses led to uncertainty about the most appropriate approach to DTG use among women of reproductive potential, affecting global DTG roll‐out plans, and limiting DTG use in adolescent girls and women. It also revealed a tension between a public health approach to antiretroviral treatment (ART) and individual choice, and highlighted difficulties interpreting and messaging an unexpected safety signal with uncertainty about risk. This difficulty was compounded by the lack of high‐quality data on pregnancy outcomes from women receiving ART outside the Tsepamo surveillance sites and countries other than Botswana, resulting in a prolonged period of uncertainty while data on additional exposures are evaluated to refute or confirm the initial safety signal. We discuss principles for evaluating and introducing new drugs in the general population that would ensure collection of appropriate data to inform drug safety in adolescent girls and women of reproductive potential and minimize confusion about drug use in this population when a safety signal is identified.ConclusionsThe response to a signal suggesting a possible safety risk for a drug used in pregnancy or among women who may become pregnant needs to be rapid and comprehensive. It requires the existence of appropriately designed surveillance systems with broad population coverage; data analyses that examine risk‐benefit trade‐offs in a variety of contexts; guidance to transform this risk‐benefit balance into effective and agreed‐upon policy; involvement of the affected community and other key stakeholders; and a communication plan for all levels of knowledge and complexity. Implementation of this proposed framework for responding to safety signals is needed to ensure that any drug used in pregnancy can be rapidly and appropriately evaluated should a serious safety alert arise.

The critical need for clinical decision support systems for identification and management of teratogenic medications

ObjectivesTo describe the critical need for clinical decision support systems to identify and manage use of potentially teratogenic medications in women of reproductive potential in the United States. Data sourcesMedline, CINAHL Plus, Academic Search Complete, International Pharmaceutical Abstracts, and the Cochrane Library databases were searched on November 1, 2018, with the key words (teratogen* OR birth defect OR Category D OR Category X OR (pregnancy or pregnant)) AND (clinical decision support OR decision support OR electronic record) to identify primary literature published in peer-reviewed journals describing clinical decision support systems implemented in outpatient settings in the United States to promote safe prescribing and clinician counseling for teratogenic medications. A hand search of the reference lists of relevant articles, including review articles, found through this search strategy was also performed. SummaryDespite the great potential for clinical decision support to assist clinicians in minimizing inadvertent fetal exposure to potentially teratogenic medications, there were only seven primary articles meeting the criteria. The results of these studies have shown some evidence of effectiveness yet had several notable limitations. No published clinical decision system showed great success. An eighth article, published in 2017, details the design of an intervention that had been implemented but not yet evaluated. ConclusionThere is a relative paucity of data regarding clinical decision support systems focused on teratogenic medications in the outpatient setting in the United States. Additional clinical decision support systems in this area need to be developed.

First Trimester Exposure to Quetiapine Appears to Be Safe

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessFirst Trimester Exposure to Quetiapine Appears to Be SafeMark MoranMark MoranSearch for more papers by this authorPublished Online:19 Oct 2018https://doi.org/10.1176/appi.pn.2018.9b14AbstractThe findings came from an ongoing study at Massachusetts General Hospital on the reproductive safety of second-generation antipsychotics.Use of the antipsychotic quetiapine during pregnancy does not appear to increase the risk of major malformations in offspring, according to a report published August 16 in AJP in Advance.Lee Cohen, M.D., director of the MGH Center for Women’s Mental Health, says that the study results confirm previous research showing no strong association between SGA exposure and major birth defects.A comparison of offspring born to a small sample of women who were using the antipsychotic in the first trimester of pregnancy with those of women unexposed to quetiapine indicated no increased risk of major malformations. “Given the considerable use of quetiapine among women of reproductive age across multiple indications, it is critical to have better information regarding the potential risks of fetal exposure to this medication so that women can make informed treatment decisions consistent with their personal wishes and the severity of their underlying psychiatric disorder,” wrote Lee Cohen, M.D., of Harvard Medical School and colleagues. “The study results suggest that quetiapine is not a major teratogen.”Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital and the Edmund and Carroll Carpenter Chair in Psychiatry in Women’s Mental Health at Harvard Medical School.The team analyzed data from the National Pregnancy Registry for Atypical Antipsychotics (NPRAA) to quantify the relative risk of major malformations associated with first-trimester exposure to quetiapine compared with women with psychiatric disorders not taking second-generation antipsychotics.As part of participation in the registry, pregnant women aged 18 to 45 with a history of psychiatric illness were interviewed across pregnancy and the early postpartum period by telephone. Obstetric, labor, and delivery medical records and medical records from the first six months of life were screened for evidence of major malformations.Of 152 women exposed to quetiapine during the first trimester, three gave birth to twins, resulting in 155 exposed live births. Among the 205 control women with available data, five sets of twins were born, resulting in 210 live births.The primary outcome was the presence of a major malformation identified within six months of birth. A major malformation was defined as a structural abnormality with surgical, medical, or cosmetic importance.Two major malformations were reported among infants with exposure to quetiapine: one infant with transposition of the great arteries and one infant with pulmonary stenosis due to dysplastic pulmonary valve. In the control group, three major malformations were reported: one infant with midshaft hypospadias requiring surgical repair, one infant with isolated cleft lip and palate, and one infant with a thickened pulmonary valve associated with mild pulmonary stenosis.“The data from this analysis are consistent with the existing literature, which does not suggest a strong association between fetal exposure to second-generation antipsychotics and an increase in the rates of major malformations,” Cohen and colleagues wrote. The NPRAA at Massachusetts General Hospital was established in 2008 to increase the availability of systematically gathered reproductive safety data for second-generation antipsychotics. The primary aim of the NPRAA is to delineate the risk of major malformations following in utero exposure to second-generation antipsychotics compared with a control group of women with psychiatric disorders who did not use agents in this drug class during pregnancy.Analysis of reproductive safety data is timely given recent changes in Food and Drug Administration (FDA) regulations governing product labeling incorporated as part of the Pregnancy and Lactation Labeling Rule. That rule, which went into effect in 2015, requires narrative explanations of pregnancy risks associated with a medication with supportive data. (The previous labeling involved a grading system that was regarded as simplistic and misleading.) The regulations apply to new medications as well as approved products as new information becomes available. “These findings represent preliminary yet important data with profound clinical implications for pregnant women and women of reproductive potential,” Cohen and colleagues wrote. “It is imperative that research efforts continue to focus on the reproductive safety of psychiatric medications that are commonly used by women during their childbearing years.” ■“Risk of Major Malformations in Infants Following First Trimester Exposure to Quetiapine” can be acccessed here. ISSUES NewArchived

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for vitamin B6

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for vitamin B6

Wishful thinking is not effective contraception: family planning, contraception, and safe prescribing.

Unplanned pregnancies account for approximately 50% of pregnancies in the United States and 40% globally. Therefore, it is good clinical practice to treat women of reproductive potential with the idea in mind that they may become pregnant during the course of treatment, regardless of their stated intentions. In psychiatry, most of the disorders we treat are chronic or recurrent; women are often on psychotropic medications during the reproductive years, and many will require pharmacologic treatment for psychiatric illnesses during pregnancy.

Lomitapide, mipomersen: Two novel agents for homozygous familial hypercholesterolemia

Lomitapide, mipomersen: Two novel agents for homozygous familial hypercholesterolemia