Syphilis in pregnancy: an ongoing public health threat.

Syphilis is a treponemal infection that can be acquired sexually, hematogenously, or via vertical transmission from mother to infant. Despite evidence-based curative treatment options with penicillin, it remains a public health threat with increasing prevalence over recent years. Congenital syphilis, a condition where a fetus acquires the infection during pregnancy, can lead to stillbirth, miscarriage, preterm birth, birth defects, and lifelong physical or neurologic changes. Congenital syphilis rates in the United States increased by 261% from 2013 to 2018 and continue to increase in 2021. The only recommended treatment for syphilis in pregnancy is benzathine penicillin G because evidence of decreased risk of congenital syphilis with other modalities is lacking. Testing for syphilis is complex and includes either the reverse-sequence algorithm or the traditional algorithm. Determination of the clinical stage of syphilis includes incorporation of the previous treatment sequence and physical examination. The goal of this review was to discuss the current evidence about optimal treatment and testing during pregnancy to optimize maternal health and prevent congenital syphilis.

Omphalocele-What should we tell the prospective parents?

An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%-32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith-Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization.

Predicting Placenta Accreta Spectrum: Validation of the Placenta Accreta Index.

OBJECTIVES: The placenta accreta spectrum (PAS) incidence has risen substantially over the past century, paralleling a rise in cesarean delivery (CD) rates. Prenatal diagnosis of PAS improves maternal outcomes. The Placenta Accreta Index (PAI) is a standardized approach to prenatal diagnosis of PAS incorporating clinical risk and ultrasound (US) findings suggestive of placental invasion. We sought to validate the PAI for prediction of PAS in pregnancies with prior CD. METHODS: This work was a retrospective cohort study of pregnancies with 1 or more prior CDs that received a US diagnosis of placenta previa or low-lying placenta in the third trimester. Images of third-trimester US with a complete placental evaluation were read by 2 blinded physicians, and the PAI was applied. Surgical outcomes and pathologic findings were reviewed. Placenta accreta spectrum was diagnosed if clinical evidence of invasion was seen at time of delivery or if any placental invasion was identified histologically. International Federation of Gynecology and Obstetrics criteria were used. RESULTS: A total of 194 women met inclusion criteria. Cesarean hysterectomy was performed in 92 (47%), CD in 97 (50%), and vaginal delivery in 5 (3%). Of those who underwent hysterectomy, PAS was histologically confirmed in 79 (85%) pregnancies. Of the remaining 13 who underwent hysterectomy, all met International Federation of Gynecology and Obstetrics grade 1 clinical criteria for PAS. With a threshold of greater than 4, the PAI has a sensitivity of 87%, specificity of 77%, positive predictive value of 72%, and negative predictive value of 90% for PAS diagnosis. CONCLUSIONS: Contemporaneous application of the PAI, a standardized approach to US diagnosis, is useful in the prenatal prediction of PAS.

Congenital syphilis: A contemporary update on an ancient disease.

Congenital syphilis (CS) rates reached a 20-year high in the United States in 2018. Unlike previous years, most babies diagnosed with CS were born to mothers who received prenatal care, indicative of the need for better provider education and guideline adherence. Current rates suggest that screening for syphilis should be performed at the first prenatal care visit and twice during the third trimester. There are two diagnostic algorithms available for use in the United States (traditional and reverse) and providers must understand how to perform each algorithm. Treatment should be administered according to stage of syphilis per Centers for Disease Control recommendations with best neonatal outcomes seen when treatment is initiated >30 days before delivery. Benzathine Penicillin G remains the only recommended treatment of syphilis during pregnancy. In viable pregnancies, a pretreatment ultrasound is recommended to identify sonographic evidence of fetal infection and treatment should be initiated with continuous fetal monitoring to evaluate for the Jarisch-Herxheimer reaction which can cause preterm labor and fetal distress. After adequate syphilotherapy, a fourfold decline in maternal nontreponemal titers may not be observed by delivery and does not correlate with rates of CS.

Prospective First-Trimester Ultrasound Imaging of Low Implantation and Placenta Accreta Spectrum.

OBJECTIVES: To prospectively evaluate low implantation of the gestational sac and other first-trimester ultrasound (US) parameters for prediction of placenta accreta spectrum (PAS). METHODS: Women with a diagnosis of low implantation on clinically indicated first-trimester US underwent a transvaginal US examination at 10 to 13 weeks' gestation to assess the trophoblast location, anechoic areas, bridging vessels, and smallest myometrial thickness (SMT). The placental location was evaluated in the second trimester, and serial US examinations were performed in cases of low placentation. Placenta accreta spectrum was based on clinical findings and confirmed by histologic results. RESULTS: Of 68 women, 40 (59%) had prior cesarean delivery (CD). Hysterectomy was performed in 8, all with prior CD. Of these, 7 (88%) had US suspicion of PAS. In 16 with prior CD and basalis overlying the internal os, 9 (56%) had second-trimester placenta previa, and 7 of 9 (78%) underwent hysterectomy with pathologic confirmation of PAS. Of 28 without prior CD, there were no cases of persistent low placentation in the third trimester regardless of the trophoblast location. Ultrasound parameters associated with PAS were a smaller distance from the inferior trophoblastic border to the external os, disruption of the bladder-serosal interface, bridging vessels, anechoic areas, and the SMT. In women with prior CD, use of the SMT in the sagittal plane yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval, 0.91-1.00). CONCLUSIONS: First-trimester low implantation increases the risk of persistent placenta previa and PAS in women with prior CD. All parameters were associated with PAS, the most predictive being the SMT.

Maternal outcomes in unexpected placenta accreta spectrum disorders: single-center experience with a multidisciplinary team.

OBJECTIVE: In a 2015 Maternal-Fetal Medicine Units Network study, only half of placenta accreta spectrum cases were suspected before delivery, and the outcomes in the anticipated cases were paradoxically poorer than in unanticipated placenta accreta spectrum cases. This was possibly because the antenatally suspected cases were of greater severity. We sought to compare the outcomes of expected vs unexpected placenta accreta spectrum in a single large US center with multidisciplinary management protocol. STUDY DESIGN: This was a retrospective cohort study carried out between Jan. 1, 2011, and June 30, 2018, of all histology-proven placenta accreta spectrum deliveries in an academic referral center. Patients diagnosed at the time of delivery were cases (unexpected placenta accreta spectrum), and those who were antentally diagnosed were controls (expected placenta accreta spectrume). The primary and secondary outcomes were the estimated blood loss and the number of red blood cell units transfused, respectively. Variables are reported as median and interquartile range or number (percentage). Analyses were made using appropriate parametric and nonparametric tests. RESULTS: Fifty-four of the 243 patients (22.2%) were in the unexpected placenta accreta spectrum group. Patients in the expected placenta accreta spectrum group had a higher rate of previous cesarean delivery (170 of 189 [89.9%] vs 35 of 54 [64.8%]; P < .001) and placenta previa (135 [74.6%] vs 19 [37.3%]; P < .001). There was a higher proportion of increta/percreta in expected placenta accreta spectrum vs unexpected placenta accreta spectrum (125 [66.1%] vs 9 [16.7%], P < .001). Both primary outcomes were higher in the unexpected placenta accreta spectrum group (estimated blood loss, 2.4 L [1.4-3] vs 1.7 L [1.2-3], P = .04; red blood cell units, 4 [1-6] vs 2 [0-5], P = .03). CONCLUSION: Our data contradict the Maternal-Fetal Medicine Units results and instead show better outcomes in the expected placenta accreta spectrum group, despite a high proportion of women with more severe placental invasion. We attribute this to our multidisciplinary approach and ongoing process improvement in the management of expected cases. The presence of an experienced team appears to be a more important determinant of maternal morbidity in placenta accreta spectrum than the depth of placental invasion.

Challenges in the Contemporary Management of Syphilis among Pregnant Women in New Orleans, LA.

Objective: The aim of this retrospective review is to evaluate trends in the management of maternal and congenital syphilis (CS) in a tertiary care center in New Orleans, LA. Study Design: All cases of maternal and neonatal syphilis over a five year period at Touro Infirmary, New Orleans, LA, were identified using ICD-9/10 codes. Charts were reviewed for demographic and obstetrical variables, stage of syphilis at diagnosis, lab values, and treatment regimen. Newborn treatment and other outcomes were recorded. Results: During the study period 106 infected mother-baby pairs were identified. Of these, 73 charts are available for review. 41% (n = 30) of women received inadequate therapy according to their stage of disease. 9% of newborns (n = 6) were found to be symptomatic for CS; however, only 83.3% of these were admitted to the neonatal intensive care unit. Only 20% (n = 6) of infants were adequately treated with an extended penicillin regimen if the mother was not adequately treated. Furthermore, only 63.0% of newborns had a nontreponemal titer performed. Conclusion: With rising rates of CS, strict adherence to the 2015 CDC guidelines for treatment of syphilis must be maintained.

Clinical Importance of Placental Testing among Suspected Cases of Congenital Zika Syndrome.

Contemporaneous Zika virus (ZIKV) strains can cause congenital Zika syndrome (CZS). Current ZIKV clinical laboratory testing strategies are limited and include IgM serology (which may wane 12 weeks after initial exposure) and nucleic acid testing (NAT) of maternal serum, urine, and placenta for (+) strand ZIKV RNA (which is often transient). The objectives of this study were to determine if use of additional molecular tools, such as quantitative PCR and microscopy, would add to the diagnostic value of current standard placental ZIKV testing in cases with maternal endemic exposure and indeterminate testing. ZIKV RNA was quantified from dissected sections of placental villi, chorioamnion sections, and full cross-sections of umbilical cord in all cases examined. Quantitation with high-resolution automated electrophoresis determined relative amounts of precisely verified ZIKV (74-nt amplicons). In order to localize and visualize stable and actively replicating placental ZIKV in situ, labeling of flaviviridae glycoprotein, RNA ISH against both (+) and (⁻) ZIKV-specific ssRNA strands, and independent histologic examination for significant pathologic changes were employed. We demonstrate that the use of these molecular tools added to the diagnostic value of placental ZIKV testing among suspected cases of congenital Zika syndrome with poorly ascribed maternal endemic exposure.

Syphilis during pregnancy: a preventable threat to maternal-fetal health.

Syphilis remains the most common congenital infection worldwide and has tremendous consequences for the mother and her developing fetus if left untreated. Recently, there has been an increase in the number of congenital syphilis cases in the United States. Thus, recognition and appropriate treatment of reproductive-age women must be a priority. Testing should be performed at initiation of prenatal care and twice during the third trimester in high-risk patients. There are 2 diagnostic algorithms available and physicians should be aware of which algorithm is utilized by their testing laboratory. Women testing positive for syphilis should undergo a history and physical exam as well as testing for other sexually transmitted infections, including HIV. Serofast syphilis can occur in patients with previous adequate treatment but persistent low nontreponemal titers (<1:8). Syphilis can infect the fetus in all stages of the disease regardless of trimester and can sometimes be detected with ultrasound >20 weeks. The most common findings include hepatomegaly and placentomegaly, but also elevated peak systolic velocity in the middle cerebral artery (indicative of fetal anemia), ascites, and hydrops fetalis. Pregnancies with ultrasound abnormalities are at higher risk of compromise during syphilotherapy as well as fetal treatment failure. Thus, we recommend a pretreatment ultrasound in viable pregnancies when feasible. The only recommended treatment during pregnancy is benzathine penicillin G and it should be administered according to maternal stage of infection per Centers for Disease Control and Prevention guidelines. Women with a penicillin allergy should be desensitized and then treated with penicillin appropriate for their stage of syphilis. The Jarisch-Herxheimer reaction occurs in up to 44% of gravidas and can cause contractions, fetal heart rate abnormalities, and even stillbirth in the most severely affected pregnancies. We recommend all viable pregnancies receive the first dose of benzathine penicillin G in a labor and delivery department under continuous fetal monitoring for at least 24 hours. Thereafter, the remaining benzathine penicillin G doses can be given in an outpatient setting. The rate of maternal titer decline is not tied to pregnancy outcomes. Therefore, after adequate syphilotherapy, maternal titers should be checked monthly to ensure they are not increasing four-fold, as this may indicate reinfection or treatment failure.

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

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.

Multidisciplinary team learning in the management of the morbidly adherent placenta: outcome improvements over time.

BACKGROUND: Morbidly adherent placenta (MAP) is a serious obstetric complication causing mortality and morbidity. OBJECTIVE: To evaluate whether outcomes of patients with MAP improve with increasing experience within a well-established multidisciplinary team at a single referral center. STUDY DESIGN: All singleton pregnancies with pathology-confirmed MAP (including placenta accreta, increta, or percreta) managed by a multidisciplinary team between January 2011 and August 2016 were included in this retrospective study. Turnover of team members was minimal, and cases were divided into 2 time periods so as to compare 2 similarly sized groups: T1 = January 2011 to April 2014 and T2 = May 2014 to August 2016. Outcome variables were estimated blood loss, units of red blood cell transfused, volume of crystalloid transfused, massive transfusion protocol activation, ureter and bowel injury, and neonatal birth weight. Comparisons and adjustments were made by use of the Student t test, Mann-Whitney U test, χ2 test, analysis of covariance, and multinomial logistic regression. RESULTS: A total of 118 singleton pregnancies, 59 in T1 and 59 in T2, were managed during the study period. Baseline patient characteristics were not statistically significant. Forty-eight of 59 (81.4%) patients in T1 and 42 of 59 (71.2%) patients in T2 were diagnosed with placenta increta/percreta. The median [interquartile range] estimated blood loss (T1: 2000 [1475-3000] vs T2: 1500 [1000-2700], P = .04), median red blood cell transfusion units (T1: 2.5 [0-7] vs T2: 1 [0-4], P = .02), and median crystalloid transfusion volume (T1: 4200 [3600-5000] vs T2: 3400 [3000-4000], P < .01) were significantly less in T2. Also, a massive transfusion protocol was instituted more frequently in T1: 15/59 (25.4%) vs 3/59 (5.1%); P < .01. Neonatal outcomes and surgical complications were similar between the 2 groups. CONCLUSION: Our study shows that patient outcomes are improved over time with increasing experience within a well-established multidisciplinary team performing 2-3 cases per month. This suggests that small, collective changes in team dynamics lead to continuous improvement of clinical outcomes. These findings support the development of centers of excellence for MAP staffed by stable, core multidisciplinary teams, which should perform a significant number of these procedures on an ongoing basis.

Cervical Length in Patients at Risk for Placenta Accreta.

OBJECTIVES: To evaluate cervical length measurements in women with placenta accreta compared to women with a nonadherent low-lying placenta or placenta previa and evaluate this relationship in terms of vaginal bleeding, preterm labor, and preterm birth. METHODS: We conducted a retrospective cohort study between 1997 and 2011 of gravidas with more than 1 prior cesarean delivery who had a transvaginal ultrasound examination between 24 and 34 weeks for a low-lying placenta or placenta previa. Cervical length was measured from archived images in accordance with national guidelines by a single investigator, who was blinded to outcomes and ultrasound reports. The diagnosis of placental accreta was based on histologic confirmation. For study purposes, preterm birth was defined as less than 36 weeks, and cervical lengths of 3 cm or less were considered short. Standard statistical analyses were used. RESULTS: A total of 125 patients met inclusion criteria. The cohort was divided into patients with (n = 43 [34%]) and without (n = 82 [66%]) placenta accreta and stratified by gestational age at the ultrasound examinations. Women with placenta accreta had shorter cervical length measurements during their 32- to 34-week ultrasound examinations (mean ± SD, 3.23 ± 0.98 versus 3.95 ± 1.0 cm; P < .01) and were more likely to have a short cervix of 3 cm or less (P = .001). However, these findings did not correlate with the degree of invasion (P = .3), or higher rates of vaginal bleeding and preterm labor (P = .19) resulting in preterm birth before 36 weeks (P = .64). CONCLUSIONS: Women with placenta accreta had shorter cervical lengths at 32 to 34 weeks than women with a nonadherent low-lying placenta or placenta previa, but this finding did not correlate with a higher risk of vaginal bleeding or preterm labor resulting in preterm birth before 36 weeks.

Sonographic Findings of Morbidly Adherent Placenta in the First Trimester.

OBJECTIVES: The purpose of this study was to evaluate the association between first-trimester sonographic findings and morbidly adherent placenta at delivery. METHODS: We conducted a retrospective review of all first-trimester sonographic examinations from pregnancies that underwent third-trimester sonography for placenta previa or low-lying placenta between September 1997 and October 2011. Only women with a prior cesarean delivery were included. Transabdominal and transvaginal images from these first-trimester studies were reviewed for the following sonographic parameters: distance from the inferior border of the gestational sac to the external cervical os, location of the decidua basalis, presence of anechoic areas, uterine-bladder interface irregularity, and smallest anterior myometrial thickness. Morbidly adherent placentation was confirmed on histologic examination of hysterectomy specimens. Statistical methods included univariate and multivariate analyses. RESULTS: Thirty-nine patients met inclusion criteria, of whom 14 (36%) had confirmed placental invasion. The number of prior cesarean deliveries was significantly associated with placental invasion (P < .0001). The only first-trimester sonographic finding associated with invasion was the smallest anterior myometrial thickness measured in the sagittal plane (P < .02). Multivariate analysis based on these two variables yielded an area under the receiver operating characteristic curve of 0.94 (95% confidence interval, 0.87-1.00) and significantly improved the prediction of placental invasion compared to using the number of prior cesarean deliveries alone. CONCLUSIONS: In women with persistent placenta previa or low-lying placenta and prior cesarean delivery, the smallest anterior myometrial thickness on first-trimester sonography significantly improved detection of morbidly adherent placenta.

Maternal titers after adequate syphilotherapy during pregnancy.

BACKGROUND: We aimed to construct a timeline for nontreponemal titer decline specific to pregnancy and evaluate factors associated with inadequate decline by delivery. METHODS: This was a retrospective medical records review from September 1984 to June 2011 of women diagnosed with syphilis after 18 weeks of gestation. Women were treated according to stage of syphilis per Centers for Disease Control and Prevention guidelines. Patients with both pretreatment and delivery titers were included for data analysis. Demographics, stage of syphilis, maternal titers, delivery, and infant outcomes were recorded. Standard statistical analyses were performed for categorical and continuous data. The titer decline was analyzed using mixed-effects regression modeling. RESULTS: A total of 166 patients met inclusion criteria. Mean gestational age at treatment was 29.1 ± 5 weeks, and 93 (56%) women were diagnosed with early-stage syphilis. For all stages of syphilis, maternal titers declined after syphilotherapy. Pretreatment titers were higher and declined more rapidly in primary and secondary disease than in latent-stage disease and syphilis of unknown duration. Sixty-three (38%) patients achieved a 4-fold decline by delivery. Patients without a 4-fold decline by delivery were older (24.6 vs 21.5 years; P < .001), treated later in pregnancy (30.3 vs 27.3 weeks; P < .001), diagnosed with latent syphilis or syphilis of unknown duration, and had less time from treatment to delivery (7.8 vs 11.1 weeks; P < .001). CONCLUSIONS: Maternal serologic response during pregnancy after adequate syphilotherapy varied by stage of disease. Failure to achieve a 4-fold decline in titers by delivery is more a reflection of treatment timing than of treatment failure.

Ultrasound predictors of placental invasion: the Placenta Accreta Index.

OBJECTIVE: We sought to apply a standardized evaluation of ultrasound parameters for the prediction of placental invasion in a high-risk population. STUDY DESIGN: This was a retrospective review of gravidas with ≥1 prior cesarean delivery who received an ultrasound diagnosis of placenta previa or low-lying placenta in the third trimester at our institution from 1997 through 2011. Sonographic images were reviewed by an investigator blinded to pregnancy outcome and sonography reports. Parameters assessed included loss of retroplacental clear zone, irregularity and width of uterine-bladder interface, smallest myometrial thickness, presence of lacunar spaces, and bridging vessels. Diagnosis of placental invasion was based on histologic confirmation. Statistical analyses were performed using linear logistic regression and multiparametric analyses to generate a predictive equation evaluated using a receiver operating characteristic curve. RESULTS: Of 184 gravidas who met inclusion criteria, 54 (29%) had invasion confirmed on hysterectomy specimen. All sonographic parameters were associated with placental invasion (P < .001). Constructing a receiver operating characteristic curve, the combination of smallest sagittal myometrial thickness, lacunae, and bridging vessels, in addition to number of cesarean deliveries and placental location, yielded an area under the curve of 0.87 (95% confidence interval, 0.80-0.95). Using logistic regression, a predictive equation was generated, termed the "Placenta Accreta Index." Each parameter was weighted to create a 9-point scale in which a score of 0-9 provided a probability of invasion that ranged from 2-96%, respectively. CONCLUSION: Assignment of the Placenta Accreta Index may be helpful in predicting individual patient risk for morbidly adherent placenta.