Joan Mastrobattista

Is There Evidence for Potential Harm of Electronic Cigarette Use in Pregnancy

BACKGROUND Use of electronic cigarettes (e-cigarettes) and other nicotine containing products is increasing among women of reproductive age. The short- and long-term effects of these products on both mother and fetus are unknown. METHODS Because e-cigarettes are nicotine delivery systems, we sought to conduct a comprehensive review of the effects of nicotine on the fetus. RESULTS In utero nicotine exposure in animal models is associated with adverse effects for the offspring lung, cardiovascular system and brain. In the lung, this included reduced surface area, weight, and volume, as well as emphysema-like lesions. In adulthood, exposed offspring demonstrate elevated blood pressure and increased perivascular adipose tissue. In the brain, exposure alters offspring serotonergic, dopaminergic, and norepinephrine networks, which in turn are associated with behavioral and cognitive impairments. We also review current data on the lack of efficacy of nicotine replacement therapy in pregnant women, and highlight different nicotine containing products such as snuff, snus, and hookah. CONCLUSION We conclude that no amount of nicotine is known to be safe during pregnancy, and studies specifically addressing this risk are crucial and an imminent public health issue.

A qualitative assessment of the perceived risks of electronic cigarette and hookah use in pregnancy

BackgroundStudies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy.MethodsEleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes.ResultsAnalyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is “Blu.” In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus.ConclusionsAlthough a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e-cigarette use will not carry the same stigma as regular cigarette smoking in pregnancy. In addition, the impression of e-cigarettes as a healthier alternative to smoking may influence use in pregnancy. Clinicians need to be prepared for questions of e-cigarette safety and efficacy as smoking cessation devices from their pregnant patients who smoke, and women who smoke and are planning to become pregnant.

Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic

&NA; Zika virus is an emerging mosquito‐borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard‐hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4–5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular‐ and sonographic‐based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross‐reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal‐fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound‐based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development.

In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model

BACKGROUND Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure METHODS Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group). RESULTS We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038). CONCLUSION We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

Impact of USPSTF recommendations for aspirin for prevention of recurrent preeclampsia

Background The US Preventive Services Task Force recommends low‐dose aspirin for the prevention of preeclampsia among women at high risk for primary occurrence or recurrence of disease. Recommendations for the use of aspirin for preeclampsia prevention were issued by the US Preventive Services Task Force in September 2014. Objectives The objective of the study was to evaluate the incidence of recurrent preeclampsia in our cohort before and after the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Study Design This was a retrospective cohort study designed to evaluate the rates of recurrent preeclampsia among women with a history of preeclampsia. We utilized a 2‐hospital, single academic institution database from August 2011 through June 2016. We excluded multiple gestations and included only the first delivery for women with multiple deliveries during the study period. The cohort of women with a history of preeclampsia were divided into 2 groups, before and after the release of the US Preventive Services Task Force 2014 recommendations. Potential confounders were accounted for in multivariate analyses, and relative risk and adjusted relative risk were calculated. Results A total of 17,256 deliveries occurred during the study period. A total of 417 women had a documented history of prior preeclampsia: 284 women before and 133 women after the US Preventive Services Task Force recommendation. Comparing the before and after groups, the proportion of Hispanic women in the after group was lower and the method of payment differed between the groups (P <.0001). The prevalence of type 1 diabetes was increased in the after period, but overall rates of pregestational diabetes were similar (6.3% before vs 5.3% after [P > .05]). Risk factors for recurrent preeclampsia included maternal age >35 years (relative risk, 1.83; 95% confidence interval, 1.34–2.48), Medicaid insurance (relative risk, 2.08; 95% confidence interval, 1.15–3.78), type 2 diabetes (relative risk, 2.13; 95% confidence interval, 1.37–3.33), and chronic hypertension (relative risk, 1.96; 95% confidence interval, 1.44–2.66). The risk of recurrent preeclampsia was decreased by 30% in the after group (adjusted relative risk, 0.70; 95% confidence interval, 0.52–0.95). Conclusion Rates of recurrent preeclampsia among women with a history of preeclampsia decreased by 30% after release of the US Preventive Services Task Force recommendation for aspirin for preeclampsia prevention. Future prospective studies should include direct measures of aspirin compliance, gestational age at initiation, and explore the influence of race and ethnicity on the efficacy of this primary prevention.

The effect of body mass index on post-vaccination maternal and neonatal pertussis antibody levels

The objective was to determine if there is an association between maternal body mass index (BMI) and maternal and neonatal pertussis antibody concentrations following vaccination. This is a nested cohort study of 123 women who received the Tdap vaccine during pregnancy. Women were stratified by BMI into three groups--normal, overweight, and obese, based on first trimester or pre-pregnancy BMI. Maternal and umbilical cord serum samples were tested for post-vaccination pertussis IgG antibody. The mean maternal pertussis antibody concentration was 167.5 U/mL for normal BMI (n=29), 169.8 U/mL for overweight BMI (n=54), and 175.5 U/mL for the obese BMI groups (n=40). The mean fetal pertussis antibody concentrations were 182.3 U/mL, 191.4 U/mL, and 197.7 U/mL for these groups respectively. Seroprotection was achieved in 89.7% of neonates (26/29) in the normal BMI group, 87.0% (47/54) in the overweight BMI group, and 97.5% (39/40) in the obese BMI group. None of these differences reached statistical significance. Maternal BMI does not affect the maternal or neonatal pertussis antibody response to the Tdap vaccine in women who receive the vaccine in pregnancy. Maternal BMI is unlikely to affect the neonatal protective effects of a standard dose of Tdap vaccine in pregnancy. PRéCIS: Maternal and umbilical cord antibody response to the pertussis vaccine is not affected by maternal body mass index.

Are First Trimester Nuchal Septations Independent Risk Factors for Chromosomal Anomalies

There is conflicting information regarding the role of nuchal septations during first‐trimester genetic screening. This study was designed to determine whether nuchal septations are risk factors for chromosomal anomalies, independent of increased nuchal translucency (NT), in the first trimester of pregnancy.

Role of Maternal Serum Alpha-Fetoprotein and Ultrasonography in Contemporary Detection of Spina Bifida.

OBJECTIVE Midtrimester maternal serum alpha-fetoprotein (MSAFP) and sonographic evaluation have been used to screen for spina bifida. With the increased uptake of cell-free DNA (cfDNA) and first trimester screening, MSAFP levels may no longer be obtained routinely. Our aim was to evaluate a pediatric neurosurgical referral center database of spina bifida cases to determine the antenatal detection rate and means of diagnosis. STUDY DESIGN Nested case series of all spina bifida cases referred postnatally from 2007 to 2013. Data were abstracted from the maternal record and rates of antenatal detection with MSAFP and sonographic screening were determined. RESULTS Of the 105 postnatally referred cases, 11.4% (12/105) were not identified until delivery. Overall, 39% of the cases had MSAFP screening. The odds ratio for sonogram-based detection of spina bifida was 4.9 (95% confidence interval, 2-11.9). Of the neonatally detected cases, 100% had prenatal care and 91.6% (11 of the 12 cases) had documented sonography. CONCLUSION We have found that 11.4% of the spina bifida cases were not detected before delivery. Nine out of the 12 cases of antenatally missed spina bifida were not screened using MSAFP. Our findings support the approach of midtrimester MSAFP screening combined with sonographic evaluation. We speculate that prenatal screening with MSAFP is underutilized.

Fetal Tachycardia Is an Independent Risk Factor for Chromosomal Anomalies in First-Trimester Genetic Screening: Fetal Tachycardia and Chromosomal Anomalies

The association of an abnormal fetal heart rate (FHR) and chromosomal anomalies in the first trimester of pregnancy remains unclear, probably because of the lack of control for known confounding factors. This study was designed to determine whether an increased FHR is an independent risk factor for chromosomal anomalies between 11 and 14 weeks’ gestation.

Family Physicians’ Perceived Prevalence, Safety, and Screening for Cigarettes, Marijuana, and Electronic-Nicotine Delivery Systems (ENDS) Use during Pregnancy

Objective: Assess perceptions of prevalence, safety, and screening practices for cigarettes and secondhand smoke exposure (SHSe), marijuana (and synthetic marijuana), electronic nicotine delivery systems (ENDS; eg, e-cigarettes), nicotine-replacement therapy (NRT), and smoking-cessation medications during pregnancy, among primary care physicians (PCPs) providing obstetric care. Methods: A web-based, cross-sectional survey was e-mailed to 3750 US physicians (belonging to organizations within the Council of Academic Family Medicine Educational Research Alliance). Several research groups’ questions were included in the survey. Only physicians who reported providing “labor and delivery” obstetric care responded to questions related to the study objectives. Results: A total of 1248 physicians (of 3750) responded (33.3%) and 417 reported providing labor and delivery obstetric care. Obstetric providers (N = 417) reported cigarette (54%), marijuana (49%), and ENDS use (24%) by “Some (6% to 25%)” pregnant women, with 37% endorsing that “Very Few (1% to 5%)” pregnant women used ENDS. Providers most often selected that very few pregnant women used NRT (45%), cessation medications (ie, bupropion or varenicline; 37%), and synthetic marijuana (23%). Significant proportions chose “Do not Know” for synthetic marijuana (58%) and ENDS (27%). Over 90% of the sample perceived that use of or exposure to cigarettes (99%), synthetic marijuana (99%), SHS (97%), marijuana (92%), or ENDS (91%) were unsafe during pregnancy, with the exception of NRT (44%). Providers most consistently screened for cigarette (85%) and marijuana use (63%), followed by SHSe in the home (48%), and ENDS (33%) and synthetic marijuana use (28%). Fewer than a quarter (18%) screened consistently for all substances and SHSe. One third (32%) reported laboratory testing for marijuana and 3% reported laboratory testing for smoking status. Conclusion: This sample of PCPs providing obstetric care within academic settings perceived cigarettes, marijuana, and ENDS use to be prevalent and unsafe during pregnancy. Opportunities for increased screening during pregnancy across these substances were apparent.