A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

The Association between Prenatal Nicotine Exposure and Offspring's Hearing Impairment.

OBJECTIVE: The objective of this study is to evaluate whether there is an association between in-utero exposure to nicotine and subsequent hearing dysfunction. PATIENTS AND METHODS: Secondary analysis of a multicenter randomized trial to prevent congenital cytomegalovirus (CMV) infection among gravidas with primary CMV infection was conducted. Monthly intravenous immunoglobulin hyperimmune globulin therapy did not influence the rate of congenital CMV. Dyads with missing urine, fetal or neonatal demise, infants diagnosed with a major congenital anomaly, congenital CMV infection, or with evidence of middle ear dysfunction were excluded. The primary outcome was neonatal hearing impairment in one or more ears defined as abnormal distortion product otoacoustic emissions (DPOAEs; 1 to 8 kHz) that were measured within 42 days of birth. DPOAEs were interpreted using optimized frequency-specific level criteria. Cotinine was measured via enzyme-linked immunosorbent assay kits in maternal urine collected at enrollment and in the third trimester (mean gestational age 16.0 and 36.7 weeks, respectively). Blinded personnel ran samples in duplicates. Maternal urine cotinine >5 ng/mL at either time point was defined as in-utero exposure to nicotine. Multivariable logistic regression included variables associated with the primary outcome and with the exposure (p < 0.05) in univariate analysis. RESULTS: Of 399 enrolled patients in the original trial, 150 were included in this analysis, of whom 46 (31%) were exposed to nicotine. The primary outcome occurred in 18 (12%) newborns and was higher in nicotine-exposed infants compared with those nonexposed (15.2 vs. 10.6%, odds ratio [OR] 1.52, 95% confidence interval [CI] 0.55-4.20), but the difference was not significantly different (adjusted odds ratio [aOR] = 1.0, 95% CI 0.30-3.31). This association was similar when exposure was stratified as heavy (>100 ng/mL, aOR 0.72, 95% CI 0.15-3.51) or mild (5-100 ng/mL, aOR 1.28, 95% CI 0.33-4.95). There was no association between nicotine exposure and frequency-specific DPOAE amplitude. CONCLUSION: In a cohort of parturients with primary CMV infection, nicotine exposure was not associated with offspring hearing dysfunction assessed with DPOAEs. KEY POINTS: · Nicotine exposure was quantified from maternal urine.. · Nicotine exposure was identified in 30% of the cohort.. · Exposure was not associated with offspring hearing dysfunction..

Placental Location in Maternal-Fetal Surgery for Myelomeningocele.

INTRODUCTION: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. OBJECTIVE: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. METHODS: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. RESULTS: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. CONCLUSIONS: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.

Subsequent pregnancy outcomes after open maternal-fetal surgery for myelomeningocele.

BACKGROUND: Open maternal-fetal surgery for fetal myelomeningocele results in reduction in neonatal morbidity related to spina bifida but may be associated with fetal, neonatal, and maternal complications in subsequent pregnancies. OBJECTIVE: The objective of this study was to ascertain obstetric risk in subsequent pregnancies after open maternal-fetal surgery for fetal myelomeningocele closure. STUDY DESIGN: An international multicenter prospective observational registry created to track and report maternal, obstetric, fetal/neonatal, and subsequent pregnancy outcomes following open maternal-fetal surgery for fetal myelomeningocele was evaluated for subsequent pregnancy outcome variables. Institutional Review Board approval was obtained for the registry. RESULTS: From 693 cases of open maternal-fetal surgery for fetal myelomeningocele closure entered into the registry, 77 subsequent pregnancies in 60 women were identified. The overall live birth rate was 96.2%, with 52 pregnancies delivering beyond 20 weeks gestational age and median gestational age at delivery of 37 (36.3-37.1) weeks. The uterine rupture rate was 9.6% (n = 5), resulting in 2 fetal deaths. Maternal transfusion was required in 4 patients (7.7%). CONCLUSION: The risk of uterine rupture or dehiscence in subsequent pregnancies with associated fetal morbidity after open maternal-fetal surgery is significant, but is similar to that reported for subsequent pregnancies after classical cesarean deliveries. Future pregnancy considerations should be included in initial counseling for women contemplating open maternal-fetal surgery.

Gestational age at initiation of 17-alpha hydroxyprogesterone caproate and recurrent preterm birth.

BACKGROUND: Preterm birth is the leading cause of neonatal morbidity and mortality in nonanomalous neonates in the United States. Women with a previous early spontaneous preterm birth are at highest risk for recurrence. Weekly intramuscular 17-alpha hydroxyprogesterone caproate reduces the risk of recurrent prematurity. Although current guidelines recommend 17-alpha hydroxyprogesterone caproate initiation between 16 and 20 weeks, in clinical practice, 17-alpha hydroxyprogesterone caproate is started across a spectrum of gestational ages. OBJECTIVE: The objective of the study was to examine the relationship between the gestational age at 17-alpha hydroxyprogesterone caproate initiation and recurrent preterm birth among women with a prior spontaneous preterm birth 16-28 weeks' gestation. STUDY DESIGN: This was a retrospective cohort study of women from a single tertiary care center, 2005-2016. All women with ≥1 singleton preterm births because of a spontaneous onset of contractions, preterm prelabor rupture of membranes, or painless cervical dilation between 16 and 28 weeks followed by a subsequent singleton pregnancy treated with 17-alpha hydroxyprogesterone caproate were included. Women were grouped based on quartiles of gestational age of 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 140/7 to 161/7; quartile 2, 162/7 to 170/7; quartile 3, 171/7 to 186/7; and quartile 4, 190/7 to 275/7). Women with a gestational age of 17-alpha hydroxyprogesterone caproate initiation in quartiles 1 and 2 were considered to have early-start 17-alpha hydroxyprogesterone caproate; those in quartiles 3 and 4 were considered to have late-start 17-alpha hydroxyprogesterone caproate. The primary outcome was recurrent preterm birth <37 weeks' gestation. Secondary outcomes included recurrent preterm birth <34 and <28 weeks' gestation and composite major neonatal morbidity (diagnosis of grade III or IV intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, necrotizing enterocolitis stage II or III, or death). Gestational age at delivery was compared by quartile of 17-alpha hydroxyprogesterone caproate initiation using Kaplan-Meier survival curves and the log-rank test. Logistic regression models estimated odds ratios for the association between gestational age at 17-alpha hydroxyprogesterone caproate initiation and preterm birth <37 weeks' gestation, adjusting for demographics, prior pregnancy and antenatal characteristics. RESULTS: A total of 132 women met inclusion criteria; 52 (39.6%) experienced recurrent preterm birth <37 weeks in the studied pregnancy. 17-Alpha hydroxyprogesterone caproate was initiated at a mean 176/7 ± 2.5 weeks. Demographic and baseline characteristics were similar between women with early-start 17-alpha hydroxyprogesterone caproate (quartiles 1 and 2) compared with those with late-start 17-alpha hydroxyprogesterone caproate (quartiles 3 and 4). Women with early-start 17-alpha hydroxyprogesterone caproate trended toward lower rates of recurrent preterm birth <37 weeks compared with those with late-start 17-alpha hydroxyprogesterone caproate (41.3% vs 57.7%, P = .065). Delivery gestational age was inversely proportional to gestational age at 17-alpha hydroxyprogesterone caproate initiation (quartile 1, 374/7 weeks vs quartile 2, 365/7 vs quartile 3, 361/7 weeks vs quartile 4, 340/7, P = .007). In Kaplan-Meier survival analyses, these differences in delivery gestational age by 17-alpha hydroxyprogesterone caproate initiation quartile persisted across pregnancy (log-rank P < .001). In regression models, later initiation of 17-alpha hydroxyprogesterone caproate was significantly associated with increased odds of preterm birth <37 weeks. Women with early 17-alpha hydroxyprogesterone caproate initiation also had lower rates of major neonatal morbidity than those with later 17-alpha hydroxyprogesterone caproate initiation (1.5% vs 14.3%, P = .005). CONCLUSION: Rates of recurrent preterm birth among women with a prior spontaneous preterm birth 16-28 weeks are high. Women beginning 17-alpha hydroxyprogesterone caproate early deliver later and have improved neonatal outcomes. Clinicians should make every effort to facilitate 17-alpha hydroxyprogesterone caproate initiation at 16 weeks.

Temporal trends in maternal medical conditions and stillbirth.

OBJECTIVE: The objective of this study was to estimate the prevalence and temporal trends of medical conditions among women with stillbirth and to determine the effect of medical comorbidities on the trend of stillbirth. STUDY DESIGN: The Nationwide Inpatient Sample (NIS) for the years 2008-2010 was first queried for all delivery-related discharges. A multivariable logistic regression model was constructed with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) calculated for medical conditions among women with stillbirth. The NIS was then queried for the years 2000-2010, and the effect of maternal medical conditions on the stillbirth rate was estimated. RESULTS: From 2008 to 2010, there were 51,080 deliveries to women with stillbirth, giving a rate of 4.08 per 1000 live births. Women with stillbirth were more likely to be African American (OR, 2.12; 95% CI, 2.07-2.17), with an age less than 25 years (OR, 1.19; 95% CI, 1.16-1.22) or older than 35 years (OR, 1.40; 95% CI, 1.37-1.44) compared with women without stillbirth. Medical conditions such as cardiac, rheumatological, and renal disorders; hypertension; diabetes; thrombophilia; and drug, alcohol and tobacco use, were independent predictors of fetal demise in multivariable logistic regression modeling. From 2000 to 2010, despite an increase in the total number of births to women with comorbidities, there was a significant decrease in the stillbirth rate, which was more pronounced among women with comorbidities compared with women without comorbidities (P=.021). CONCLUSION: From 2000 to 2010, there was a significantly greater decrease in the stillbirth rate among women with maternal medical conditions than there was among women without comorbidities. These findings occurred despite an overall increase in the number of pregnancies to women with medical comorbidities over the time period. Because the NIS does not include information on gestational age, birthweight, or whether subjects had antepartum testing, we are not able to determine the effect of these variables on the observed outcomes.

Single-center serological surveillance of SARS-CoV-2 in pregnant patients presenting to labor and delivery.

OBJECTIVE: To measure maternal/fetal SARS-CoV-2 antibody levels. METHODS: A prospective observational study of eligible parturients admitted to the hospital for infant delivery was conducted between April and September 2020. SARS-CoV-2 antibody levels were measured in maternal and umbilical cord specimens using an in-house ELISA based on the receptor-binding domain (RBD) of the spike protein. Among SARS-CoV-2 seropositive patients, spike RBD antibody isotypes (IgG, IgM, and IgA) and ACE2 inhibiting antibodies were measured. RESULTS: In total, 402 mothers were enrolled and spike RBD antibodies in 388 pregnancies were measured (336 maternal and 52 cord specimens). Of them, 19 were positive (15 maternal, 4 cord) resulting in a seroprevalence estimate of 4.8% (95% confidence interval 2.9-7.4). Of the 15 positive maternal specimens, all had cord blood tested. Of the 15 paired specimens, 14 (93.3%) were concordant. Four of the 15 pairs were from symptomatic mothers, and all four showed high spike-ACE2 blocking antibody levels, compared to only 3 of 11 (27.3%) from asymptomatic mothers. CONCLUSION: A variable antibody response to SARS-CoV-2 in pregnancy among asymptomatic infections compared to symptomatic infections was found, the significance of which is unknown. Although transfer of transplacental neutralizing antibodies occurred, additional research is needed to determine how long maternal antibodies can protect the infant against SARS-CoV-2 infection.

Elevated midtrimester maternal plasma cytokines and preterm birth in patients with cerclage.

BACKGROUND: Cerclage is used for the prevention of spontaneous preterm birth; however, many patients at high risk of spontaneous preterm birth who have a cerclage in place eventually deliver before term. Although inflammation, measured by biomarkers (eg, cytokines), is a known risk factor for preterm delivery, evaluation of inflammation to determine pregnancy outcomes among patients with cerclage is poorly understood. OBJECTIVE: We sought to examine levels of maternal plasma inflammatory cytokines in the midtrimester among asymptomatic patients with a cervical cerclage (placed for any indication, including history, ultrasound, and examination indications) to evaluate the association between cytokine levels and preterm birth. STUDY DESIGN: This was a prospective cohort study of singleton, nonanomalous pregnancies who had a cerclage placed at <24 weeks of gestation from 2015 to 2018 at a single tertiary institution. Maternal plasma was collected perioperatively whenever possible. A custom magnetic bead Luminex cytokine assay was used to measure plasma inflammatory cytokine levels from these stored samples. The primary outcome was preterm birth at <37 weeks of gestation. A statistical cut point was calculated for each cytokine level to assess its optimal sensitivity and specificity for spontaneous preterm birth prediction. Patients were classified as having a "high" or "low" result for each cytokine based on this cut point. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and positive and negative predictive values for spontaneous preterm birth prediction. Cox proportional-hazards regression modeled the association between the number of "high" inflammatory cytokines and gestational age at delivery, adjusting for confounders. Additional analyses were performed on the subgroup of patients with history-indicated cerclage and those with an ultrasound- or examination-indicated cerclage. RESULTS: A total of 43 patients participated in this study: 20 (46.5%) had spontaneous preterm birth (median, 30.9 weeks of gestation; interquartile range, 28.4-35.0). Plasma samples were collected at a median of 0 (interquartile range, -2 to 17) days concerning cerclage placement and a median of 18 (interquartile range, 13-21) weeks of gestation. Based on the statistical cut point for each cytokine level, 7% of patients had zero, 20.9% had 1, 18.6% had 2, 20.9% had 3, and 32.6% had ≥4 "high" cytokine results. Each additional "high" cytokine level was associated with earlier delivery (hazard ratio, 1.51; 95% confidence interval, 1.25-1.81) even after controlling for ultrasound- or examination-indication for cerclage (hazard ratio, 1.73; 95% confidence interval, 0.95-3.15). The presence of ≥4 "high" cytokine levels was 70% sensitive and 74% specific for predicting spontaneous preterm birth (area under the curve, 0.846; 95% confidence interval, 0.728-0.964; positive predictive value, 70%; negative predictive value, 73.9%). CONCLUSION: Among patients with a cervical cerclage, elevated midtrimester maternal plasma cytokine profiles were associated with subsequent preterm birth and can estimate the probability of preterm birth. Confirmation and refinement of this noninvasive panel may provide insight into improved selection of individuals who may benefit from cerclage placement and investigation of therapeutic strategies to mitigate midpregnancy inflammation.

Sociodemographic disparities as a determinant of fetal versus postnatal surgical myelomeningocele repair.

OBJECTIVE: Relatively few women undergo open maternal-fetal surgery (OMFS) for myelomeningocele (MMC) despite the potential to reverse hindbrain herniation, reduce the rate of infant shunt-dependent hydrocephalus, and improve ambulation. These benefits have the potential to significantly reduce morbidity and lifetime medical care. In this study, the authors examined demographics and socioeconomic variables of women who were offered and opted for OMFS for MMC versus postnatal MMC surgery, with the purpose of identifying variables driving the disparity between these two patient populations. METHODS: This was a retrospective case-control study of patients who underwent evaluation for OMFS for MMC at a single academic hospital from 2015 to 2020. Race/ethnicity, primary insurance type, zip code, and BMI were collected and compared by treatment received and eligibility status for OMFS. Prevalence odds ratios were used to test for associations between each independent variable and the two outcomes. Logistical regression models were utilized to determine significant predictors of undergoing OMFS and being eligible for OMFS. RESULTS: Of 96 women, 36 underwent OMFS for MMC, 40 received postnatal repair, and 20 either terminated the pregnancy or received care at another institution. Overall, 66 (68.8%) women were White, 14 (14.6%) were Black, 13 (13.5%) were Hispanic/Latinx, 1 (1.0%) was Asian, and 2 (2.1%) identified as other or multiple races. Among women who underwent OMFS for MMC, 27 (75.0%) were White, 2 (5.6%) were Black, 4 (11.1%) were Hispanic/Latinx, 1 (2.8%) was Asian, and 2 (5.6%) identified as other or multiple races. Having private insurance or TRICARE was associated with higher odds of being eligible for OMFS compared with women who were uninsured or had Medicaid when accounting for race and income (OR 3.87, 95% CI 1.51-9.59). CONCLUSIONS: The population evaluated and treated for MMC was homogeneous and insufficiently representative of the population affected by the disease. This finding raises concern, as it suggests underlying barriers to formal evaluation for OMFS for MMC. Insurance status and BMI have a significant association between the access to and election of OMFS, revealing socioeconomic disparities. This was the first study to explore sociodemographic characteristics of patient populations who may be at risk for limited access to highly specialized fetal surgical care.

Noninvasive Prediction of Congenital Cytomegalovirus Infection After Maternal Primary Infection.

OBJECTIVE: To develop and internally validate a noninvasive method for the prediction of congenital cytomegalovirus (CMV) infection after primary maternal CMV infection. METHODS: We conducted a secondary analysis of a multicenter randomized placebo-controlled trial of CMV hyperimmune globulin to prevent congenital infection. Women were eligible if they had primary CMV infection, defined as detectable plasma CMV-specific immunoglobulin (Ig)M and CMV-specific IgG with avidity less than 50% before 24 weeks of gestation or IgG seroconversion before 28 weeks, and were carrying a singleton fetus without ultrasonographic findings suggestive of CMV infection. Antibody assays were performed in a single reference laboratory. Congenital infection was defined as CMV detection in amniotic fluid, neonatal urine or saliva, or postmortem tissue. Using backward elimination, we developed logit models for prediction of congenital infection using factors known at randomization. The performance of the model was assessed using leave-one-out cross-validation (a method of internal validation). RESULTS: Of 399 women enrolled in the trial, 344 (86%) had informative data for this analysis. Congenital infection occurred in 68 pregnancies (20%). The best performing model included government-assisted insurance, IgM index 4.5 or higher, IgG avidity less than 32%, and whether CMV was detectable by polymerase chain reaction in maternal plasma at the time of randomization. Cross-validation showed an average area under the curve of 0.76 (95% CI 0.70-0.82), indicating moderate discriminatory ability. More parsimonious one-, two-, and three-factor models performed significantly less well than the four-factor model. Examples of prediction with the four-factor model: for a woman with government-assisted insurance, avidity less than 32%, IgM index 4.5 or higher, and detectable plasma CMV, probability of congenital infection was 0.69 (95% CI 0.53-0.82); for a woman with private insurance, avidity 32% or greater, IgM index less than 4.5, and undetectable plasma CMV, probability of infection was 0.03 (95% CI 0.02-0.07). CONCLUSION: We developed models to predict congenital CMV infection in the presence of primary maternal CMV infection and absence of ultrasonographic findings suggestive of congenital infection. These models may be useful for patient counseling and decision making.

Amniocentesis to diagnose congenital cytomegalovirus infection following maternal primary infection.

BACKGROUND: Congenital cytomegalovirus infection following maternal primary cytomegalovirus infection affects approximately 0.4% of newborns in the United States but may be hard to diagnose prenatally. OBJECTIVE: To evaluate the current sensitivity and specificity of amniocentesis in detecting congenital cytomegalovirus infection. STUDY DESIGN: Secondary analysis of a multicenter randomized placebo-controlled trial designed to evaluate whether cytomegalovirus hyperimmune globulin reduces congenital cytomegalovirus infection in neonates of individuals diagnosed with primary cytomegalovirus infection before 24 weeks of gestation. At randomization, subjects had no clinical evidence of fetal infection. Eligible subjects were randomized to monthly infusions of cytomegalovirus hyperimmune globulin or placebo until delivery. Although not required by the trial protocol, amniocentesis following randomization was permitted. The fetuses and neonates were tested for the presence of cytomegalovirus at delivery. Comparisons were made between those with and without amniocentesis and between those with cytomegalovirus-positive and negative results, using chi-square or Fisher exact test for categorical variables and the Wilcoxon rank sum test or t test for continuous variables. A P value of <.05 was considered significant. RESULTS: From 2012 to 2018, 397 subjects were included, of whom 55 (14%) underwent amniocentesis. Cytomegalovirus results were available for 53 fetuses and neonates. Fourteen amniocenteses were positive (25%). Gestational age at amniocentesis was similar between those with and without cytomegalovirus present, as was the interval between maternal diagnosis and amniocentesis. The prevalence of fetal or neonatal infection was 26% (14/53). The neonates of all 12 subjects with a positive amniocentesis and available results had cytomegalovirus infection confirmed at delivery, as did 2 neonates from the group of 41 subjects with a negative amniocentesis, with a sensitivity of 86% (95% confidence interval, 57-98), specificity of 100% (95% confidence interval, 91-100), positive predictive value of 100% (95% confidence interval, 74-100), and negative predictive value of 95% (95% confidence interval, 83-99). Amniocentesis-positive pregnancies were delivered at an earlier gestational age (37.4 vs 39.6 weeks; P<.001) and had lower birthweights (2583±749 vs 3428±608 g, P=.004) than amniocentesis-negative pregnancies. CONCLUSION: Amniocentesis results are an accurate predictor of congenital cytomegalovirus infection.

Ultrasound prediction of birthweight and growth restriction in fetal gastroschisis.

OBJECTIVE: Most ultrasound estimated fetal weight (EFW) formulas incorporate abdominal circumference, which may overstimate growth restriction in fetal gastroschisis. The aim of this study was to determine the optimal ultrasound formula for prediction of birthweight and fetal growth restriction (FGR) in gastroschisis. STUDY DESIGN: We conducted a retrospective cohort analysis of singleton fetuses with gastroschisis. Percentage of error between ultrasound EFW (performed within 2 weeks of delivery) and birthweight was calculated. Agreement between EFW by ultrasound formulas and birthweight was determined by Bland-Altman limits of agreement; concordance between ultrasound and birthweight diagnosis of FGR was evaluated with McNemar's test. RESULTS: Birthweight was best predicted by the formulas of Shepard et al and Siemer et al. Only these formulas demonstrated significant agreement with birthweight for prediction of FGR at the 5th and 10th percentiles. CONCLUSION: The formulas of Shepard et al and Siemer et al best estimate birthweight, and their use has the potential to reduce rates of overdiagnosis of FGR.

Maternal super-obesity (body mass index > or = 50) and adverse pregnancy outcomes.

OBJECTIVE: To determine if pregnancy complications are increased in super-obese (a body mass index (BMI) of 50 or more) compared to other, less obese parturients. DESIGN: Cross-sectional study. SETTING AND POPULATION: All 19,700 eligible women, including 425 (2.2%) super-obese women with singleton births between 1996 and 2007 delivering at a tertiary referral center, identified using a perinatal research database. METHODS: Bivariate and trend analyses were used to assess the relation between super-obesity and various pregnancy complications compared to other well-established BMI categories. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression techniques. MAIN OUTCOME MEASURES: Outcomes for adjusted and unadjusted analyses were small-for-gestational age (SGA) birth, large-for-gestational age (LGA) birth, preeclampsia, gestational diabetes mellitus (GDM), fetal death, preterm birth, placental abruption, cesarean delivery, and Apgar scores < 7. RESULTS: Compared to all other obese and non-obese women, super-obese women had the highest rates of preeclampsia, GDM, LGA, and cesarean delivery (all p < 0.05 for trend test). Super-obesity was also associated with a 44% reduction in SGA compared to all other women (OR 0.55, 95% confidence interval (CI) 0.40-0.76) and a 25% reduction compared to other, less obese women (OR 0.75, 95% CI 0.54-1.03). Super-obesity was positively associated with LGA, GDM, preeclampsia, cesarean delivery, and a 5-minute Apgar score < 7 compared to all other women after controlling for important confounders. CONCLUSION: Super-obesity is associated with higher rates of pregnancy complications compared to women of all other BMI classes, including other obese women.

Pneumonia in pregnancy.

OBJECTIVE: Historically, pneumonia during pregnancy has been associated with increased morbidity and mortality compared with nonpregnant women. The goal of this article is to review current literature describing pneumonia in pregnancy. This review will identify maternal risk factors, potential complications, and prenatal outcomes associated with pneumonia and describe the contemporary management of the varied causes of pneumonia in pregnancy. RESULTS: Coexisting maternal disease, including asthma and anemia, increase the risk of contracting pneumonia in pregnancy. Neonatal effects of pneumonia in pregnancy include low birth weight and increased risk of preterm birth, and serious maternal complications include respiratory failure. Community-acquired pneumonia is the most common form of pneumonia in pregnancy, with Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae accounting for most identified bacterial organisms. Beta-lactam and macrolide antibiotics are considered safe in pregnancy and are effective for most community-acquired pneumonia in pregnancy. Viral respiratory infections, including varicella, influenza, and severe acute respiratory syndrome, can be associated with maternal pneumonia. Current antiviral and respiratory therapies can reduce maternal morbidity and mortality from viral pneumonia. Influenza vaccination can reduce the prevalence of respiratory hospitalizations among pregnant women during influenza season. Pneumocystis pneumonia continues to carry significant maternal risk to an immunocompromised population. Prevention and treatment of Pneumocystis pneumonia with trimethoprim/sulfamethoxazole is effective in reducing this risk. CONCLUSIONS: Prompt diagnosis and treatment with contemporary antimicrobial therapy and intensive care unit management of respiratory compromise has reduced the maternal morbidity and mortality due to pneumonia in pregnancy. Prevention with vaccination in at-risk populations may reduce the prevalence and severity of pneumonia in pregnant women.