Janet D. Cragan

Trends and outcomes after prenatal diagnosis of congenital cardiac malformations by fetal echocardiography in a well defined birth population, Atlanta, Georgia, 1990-1994.

OBJECTIVES In this study we used a population-based approach to assess the impact of fetal echocardiography on a well defined birth population with nearly complete ascertainment of cardiac defects. BACKGROUND Although fetal echocardiography is being used more frequently in the prenatal diagnosis of congenital cardiac malformations, its impact on the diagnosis and surveillance of cardiac defects has not been described in defined populations. METHODS All stillborn and live-born infants with diagnosed cardiac defects and whose mothers resided in the metropolitan Atlanta area from January 1990 through December 1994 were ascertained through an established birth defects surveillance system. All fetuses with cardiac defects diagnosed prenatally by a pediatric of cardiac defects, diagnostic trends and adverse fetal outcomes were described. RESULTS We identified 1,589 infants with congenital cardiac malformations, for a live-birth prevalence rate of 8.1/1,000 (95% confidence interval [CI] 7.8 to 8.6). Overall, 97 (6.1%) of these cases of cardiac malformations were diagnosed prenatally. The proportion of cardiac defects diagnosed prenatally rose from 2.6% in 1990 to 12.7% in 1994, a nearly fivefold increase. The proportion of cardiac defects diagnosed prenatally during the study varied by the type of defect, from a low of 4.7% for atrial septal defects to a high of 28% for hypoplastic left heart syndrome. Prenatally diagnosed cardiac malformations were associated with a high incidence of infant mortality (30.9%, 95% CI 2.4 to 5.4) and fetal wastage (17.5%, 95% CI 6.2 to 11.3). CONCLUSIONS These data show that fetal echocardiography is being used increasingly in the prenatal diagnosis of congenital cardiac malformations in metropolitan Atlanta. Few pregnancy terminations were reported as a result of such diagnoses. However, the study had limited power (10%) to detect a meaningful decrease in birth prevalence rates for congenital heart disease. In addition, survival of infants was not improved after prenatal diagnosis with fetal echocardiography.

The Contribution of Chromosomal Abnormalities to Congenital Heart Defects: A Population-Based Study

We aimed to assess the frequency of chromosomal abnormalities among infants with congenital heart defects (CHDs) in an analysis of population-based surveillance data. We reviewed data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth-defects surveillance system, to assess the frequency of chromosomal abnormalities among live-born infants and fetal deaths with CHDs delivered from January 1, 1994, to December 31, 2005. Among 4430 infants with CHDs, 547 (12.3%) had a chromosomal abnormality. CHDs most likely to be associated with a chromosomal abnormality were interrupted aortic arch (type B and not otherwise specified; 69.2%), atrioventricular septal defect (67.2%), and double-outlet right ventricle (33.3%). The most common chromosomal abnormalities observed were trisomy 21 (52.8%), trisomy 18 (12.8%), 22q11.2 deletion (12.2%), and trisomy 13 (5.7%). In conclusion, in our study, approximately 1 in 8 infants with a CHD had a chromosomal abnormality. Clinicians should have a low threshold at which to obtain testing for chromosomal abnormalities in infants with CHDs, especially those with certain types of CHDs. Use of new technologies that have become recently available (e.g., chromosomal microarray) may increase the identified contribution of chromosomal abnormalities even further.

Pandemic Influenza and Pregnant Women: Summary of a Meeting of Experts

Pandemic Influenza: Special Considerations for Pregnant Women was a meeting convened by the Centers for Disease Control and Prevention in 2008 to obtain input from experts and key partners regarding clinical management of pregnant women and related public health actions to be taken during a pandemic. Meeting goals were to discuss issues specific to pregnant women, identify gaps in knowledge, and develop a public health approach for pregnant women in the event of a pandemic. The meeting focused on 4 main topics: prophylaxis and treatment with influenza antiviral and other medications, vaccine use, nonpharmaceutical interventions and health care planning, and communications. Participants reviewed the available evidence to guide action in each of these areas and identified areas of critical needs for future research.

Trisomies 13 and 18: Population prevalences, characteristics, and prenatal diagnosis, metropolitan Atlanta, 1994–2003

In recent years, prenatal diagnosis and elective pregnancy termination have affected the reported birth prevalence of trisomies 13 and 18. We examined the prevalence and characteristics of these conditions using 1994–2003 data from a population‐based surveillance system, the Metropolitan Atlanta Congenital Defects Program. Including fetal deaths and elective terminations increased the number of affected pregnancies by 58.7% for trisomy 13 and 72.2% for trisomy 18. Prenatal cytogenetic testing was reported in 70.8% of trisomy 13 cases and 76.1% of trisomy 18 cases. Among those with prenatal cytogenetic tests, 60.8% of trisomy 13 and 59.7% of trisomy 18 cases were electively terminated. Compared with non‐Hispanic whites, non‐Hispanic black race was associated with a decreased frequency of prenatal cytogenetic testing for both trisomy 13 and trisomy 18 (OR 0.24, 95% CI: 0.08–0.78 and OR 0.32, 95% CI: 0.14–0.69, respectively). The reported rates of prenatal cytogenetic testing remained stable throughout the period. As expected, maternal age ≥35 years was a risk factor for both conditions. However, while 67.1% (n = 55) of the trisomy 18 case mothers were ≥35 years, only 46.9% (n = 15) of the trisomy 13 case mothers were ≥35 years. Among live‐born infants, the sex ratio among trisomy 18 infants showed an increased proportion of females: 60.4% female versus 39.6% male. However, the proportion was 48.3% female and 51.7% male among fetuses that were electively terminated in the second trimester. Inclusion of pregnancies that are prenatally diagnosed is critical for accurate surveillance and population‐based analyses of these conditions. Published 2008 Wiley‐Liss, Inc.

Medications in the First Trimester of Pregnancy: Most Common Exposures and Critical Gaps in Understanding Fetal Risk

To determine which medications are most commonly used by women in the first trimester of pregnancy and identify the critical gaps in information about fetal risk for those medications.

Teratogen update: Methylene blue††

Methylene blue (MB) is a cationic thiazine dye with the chemical name tetramethylthionine chloride. It has a characteristic deep blue color in the oxidized state, but the reduced form, leukomethylene blue (LMB), is colorless. Methylene blue has been widely used in a variety of clinical settings to identify anatomic (Manhes et al., ’94; Sills and Zinkham, ’94; Barber et al., ’95) and pathologic (Derom et al., ’93; Canto et al., ’96; Lee and Sharifi, ’96) structures and to treat methemoglobinemia (Curry, ’82; Ellis et al., ’95; Yang et al., ’95). It has also been used to inactivate viruses in fresh frozen plasma (Wieding et al., ’93), to treat chronic periodontitis (Gibson et al., ’94; Ower et al., ’95), to aid in the diagnosis of and targeted therapy for cancer (Orth et al., ’95; Link et al., ’96), and, experimentally, to treat septic shock (Schneider et al., ’92; Preiser et al., ’95; Brown et al., ’96; Driscoll et al., ’96). Intraamniotic injection of MB during obstetric procedures has been associated with serious adverse effects among newborns (Table 1). More recently, teratogenic effects have been reported following the injection of MB during midtrimester amniocentesis (Table 2). This article summarizes what is known about the biological actions of MB, the results of its use in obstetrics, and the evidence for its teratogenicity.

Are Encephaloceles Neural Tube Defects

OBJECTIVE. Encephalocele is classified as a neural tube defect, but questions have been raised regarding whether its epidemiological characteristics are similar to those of other neural tube defects. DESIGN. We compared characteristics of temporal trends in, and the impact of folic acid grain fortification on, the prevalence of encephalocele, spina bifida, and anencephaly using data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system. Prevalences of encephalocele, spina bifida, and anencephaly were compared by maternal age, gender, race, birth weight, ascertainment period (1968–1981, 1982–1993, or 1994–2002), and fortification period (1994–1996 [prefortification] and 1998–2002 [postfortification]) using prevalence ratios with 95% confidence intervals. Temporal trends were assessed using Poisson and negative binomial regression models. RESULTS. Prevalence rates of encephalocele (n = 167), spina bifida (n = 650), and anencephaly (n = 431) were 1.4, 5.5, and 3.7 per 10 000 live births, respectively. Encephalocele was similar to anencephaly in showing an increased prevalence among girls and multiple gestation pregnancies and to spina bifida and anencephaly in an annual prevalence decrease between 1968 and 2002 (−1.2% for encephalocele, −4.2% for spina bifida, and −3.6% for anencephaly). With fortification, prevalence decreased for spina bifida but not significantly for encephalocele or anencephaly. CONCLUSIONS. Encephalocele shows more similarities to spina bifida or anencephaly than it shows differences with respect to characteristics, temporal trend, and impact of fortification. Additional studies should be done to explore the etiologic heterogeneity of encephalocele using better markers of folate status and a wider range of risk factors.

Effect of prenatal diagnosis on epidemiologic studies of birth defects.

Prenatal diagnostic technology makes it possible to offer women the option of electively terminating pregnancies affected by birth defects. Excluding these pregnancies from epidemiologic studies may affect study results. We explored this effect using examples from the literature. We calculated the bias in the odds ratio caused by excluding prenatally diagnosed pregnancies when the exposure of interest is not correlated with the likelihood of terminating an affected pregnancy and when it is correlated with an increase or decrease in this likelihood. We assumed that control infants did not have birth defects. When the exposure is not associated with the likelihood of a pregnancy termination, studies excluding terminations suffer a loss of precision. When the exposure is associated with an increase or decrease in this likelihood, the odds ratios are biased toward or away from the null, respectively. The magnitude of the bias will vary according to characteristics of the study population such as the prevalence of the exposure and the frequency with which prenatal diagnosis and elective termination are used. Whenever possible, pregnancies terminated after prenatal diagnosis must be included in epidemiologic studies.

Prophylaxis and Treatment of Pregnant Women for Emerging Infections and Bioterrorism Emergencies

Infectious disease emergency preparedness planners should consider the special medical issues of pregnant women.

Safety of influenza vaccination during pregnancy: A review of subsequent maternal obstetric events and findings from two recent cohort studies

Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as a barrier to vaccination. This review describes the safety of inactivated influenza vaccination during pregnancy with a focus on maternal obstetric events, including hypertensive disorders, gestational diabetes, and chorioamnionitis. Included in the review are new findings from two studies which examined the safety of seasonal inactivated influenza vaccination during pregnancy. The first study enrolled 641 pregnant women during the 2010-2011 season and prospectively followed them until delivery or pregnancy termination. The second study enrolled 1616 pregnant women during the 2010-2011 influenza season, and followed the women and their infants for six months after delivery. No associations between inactivated influenza vaccination and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or chorioamnionitis were observed in either cohort. When considered as a whole, these studies should further reassure women and clinicians that influenza vaccination during pregnancy is safe for mothers.