Stephanie L. Gaw

Clinical accuracy of abnormal cell‐free fetal DNA results for the sex chromosomes

To investigate factors associated with abnormal cell‐free DNA (cfDNA) results for sex chromosomes (SCs).

Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes

AbstractBackgroundMalaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes.MethodsThis is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12–20xa0weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants.ResultsThe 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0–1 episodes of symptomatic malaria andxa0<xa050% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥xa02 episodes of symptomatic malaria orxa0≥xa050% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80–111.6) and 4.06 (1.73–9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRRxa0=xa03.27 (1.32–8.12) and aRRxa0=xa07.07 (2.84–17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46–21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy.ConclusionHigher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes.n Trial Registration Current Controlled Trials Identifier NCT02163447

Zika Risk and Pregnancy in Clinical Practice: Ongoing Experience as the Outbreak Evolves

OBJECTIVEnTo describe a single U.S. perinatal centers ongoing experience with evaluating pregnant patients with potential exposure to Zika virus infection.nnnMETHODSnThis is an institutional review board-approved longitudinal observational study from January to August 2016 from a single perinatal referral center. Patients who had traveled to or had sexual contact with a person who traveled to a region with documented local Zika virus transmission were included in the study. The aim of the study was to identify the rate of confirmed infection among pregnant women referred to our center with established risk factors for Zika virus acquisition. We also sought to characterize travel patterns that constituted risk, to identify rates of symptoms suggesting infection, and to potentially describe findings suggestive of congenital Zika virus infection in prenatal ultrasound evaluations.nnnRESULTSnWe evaluated 185 pregnant women with potential Zika virus exposure. Testing was offered in accordance with the version of the Centers for Disease Control and Prevention guidelines in place at the time of the consultation visit. Geographic exposure data showed Mexico (44%), the Caribbean (17%), North America (16%), South America (13%), and Central America (9%) to be the most common areas in which potential exposure occurred. One hundred twenty-three (67%) patients reported insect bites and 19 (10%) patients reported symptoms. Overall, five (3% of all) patients had prenatal ultrasound findings suggestive of possible fetal Zika virus infection; all their Zika virus test results returned negative. These findings included microcephaly, echogenic intracardiac foci, and ventricular calcifications. Of the 153 Zika virus screening tests ordered, eight (5%) immunoglobulin M results returned positive or equivocal with only one positive through confirmatory testing. Overall, 1 of 185 (0.5%) of all those consulted and 1 of 153 (0.7%) of those tested had a confirmed Zika virus infection with no confirmed fetal or neonatal infections.nnnCONCLUSIONnWe identified low rates of confirmed maternal Zika virus infection in our cohort, but the number of patients described here demonstrates the magnitude of concern existing among both patients and physicians regarding possible perinatal Zika virus infection. It also underscores the need for health care providers to be prepared to answer questions, explain laboratory and ultrasound results, and describe testing options for concerned patients and their families.

Eye Findings in Infants With Suspected or Confirmed Antenatal Zika Virus Exposure.

In this study, we characterize ophthalmic manifestations of antenatal ZIKV exposure in infants who were referred for evaluation during the 2015–2016 Rio de Janeiro outbreak. BrightcoveDefaultPlayer10.1542/6138644049001PEDS-VA_2018-1104 Video Abstract OBJECTIVES: To characterize ophthalmic manifestations of confirmed or suspected antenatal Zika virus (ZIKV) exposure. METHODS: Infants with antenatal ZIKV exposure were referred for evaluation during the 2015–2016 Rio de Janeiro outbreak. Mothers with symptomatic ZIKV infection during pregnancy and/or infants with microcephaly or other findings that were suggestive of suspected antenatal exposure were tested with reverse transcriptase polymerase chain reaction (RT-PCR). Complete eye examinations were performed by pediatric ophthalmologists between January 2016 and February 2017. The main outcome measure was eye abnormalities in RT-PCR–positive and suspected (ie, not tested or RT-PCR–negative) antenatal ZIKV cases. RESULTS: Of 224 infants, 189 had RT-PCR testing performed. Of 189 patients, 156 had positive RT-PCR results in their blood, urine, and/or placenta. Of 224 infants, 90 had central nervous system (CNS) abnormalities, including microcephaly (62 infants). Eye abnormalities were present in 57 of 224 (25.4%) infants. Optic nerve (44 of 57; 77.2%) and retina abnormalities (37 of 57; 64.9%) were the most common. The group with suspected ZIKV infection (68 infants) had proportionally more eye (36.8% vs 20.5%; P = .022) and CNS abnormalities (68.3% vs 28.1%; P = .008), likely because of referral patterns. Eye abnormalities consistent with ZIKV infection were clinically comparable in both RT-PCR–positive and unconfirmed groups, including 4 RT-PCR–positive infants of 5 without any CNS abnormalities. CONCLUSIONS: Similar eye manifestations were identified regardless of laboratory confirmation. Well-appearing infants were also found to have eye abnormalities. Therefore, all infants born after ZIKV outbreaks should be universally screened for eye abnormalities.

151 – Trisomy 21

Trisomy 21 (Down syndrome) is the most common autosomal trisomy in newborns, and is strongly associated with increasing maternal age. Trisomy 21 results most commonly from maternal meiotic nondisjunction. Unbalanced translocation accounts for up to 4% of cases. Trisomy 21 has a distinct clinical phenotype and varying degrees of cognitive impairment. The majority of cases are detected prenatally, usually with a combination of maternal genetic screening and prenatal ultrasound. The most common structural abnormalities in trisomy 21 are increased nuchal translucency, cardiac defects, and duodenal atresia. Other possible ultrasound findings include thick nuchal fold, ventriculomegaly, absent or hypoplastic nasal bone, echogenic intracardiac focus, echogenic bowel, pyelectasis, and short limbs.

149 – Trisomy 13

Trisomy 13 (Patau syndrome) is the third most common autosomal trisomy in newborns. It results from an extra chromosome 13 secondary to nondisjunction or translocation. In the United States, most cases of trisomy 13 are detected prenatally, either by genetic screening or ultrasound. Greater than 90% of fetuses with trisomy 13 have findings detected on prenatal ultrasound. The most common abnormalities visualized are cardiac abnormalities, holoprosencephaly, omphalocele, and cleft lip/palate. Fetuses with trisomy 13 have a 50% risk of intrauterine fetal demise after 12 weeks of gestation. Of live-born infants, most will not survive the immediate newborn period. Those that survive have severe physical and neurocognitive deficits.

Mosaic Trisomies 8, 9, and 16

Abstract The most severe trisomies usually result in early pregnancy loss. However, some of these severe trisomies may survive to birth if they are mosaics, in which the condition only affects a portion of the cells in the body. Trisomy 8 mosaicism (Warkany syndrome 2) has a range of clinical phenotypes depending on the cell lines affected. Common findings include agenesis of the corpus callosum, hydrocephalus, ventriculomegaly, abnormal facies, cardiac malformations, and joint contractures. Children have progressive neurodevelopmental delay, although life expectancy may be normal. Trisomy 9 mosaicism is a rare disorder. Characteristic ultrasound findings include microcephaly, craniofacial defects, cardiac abnormalities, and limb findings. Most patients will die within the first year of life, and have severe intellectual and motor deficiencies. Trisomy 16 is the most common autosomal trisomy, although most will result in first-trimester pregnancy loss. All cases that survive to birth are mosaic trisomy 16. Ultrasound findings include cardiac anomalies, pulmonary hypoplasia, genitounrinary anomalies, growth restriction, and two-vessel umbilical cord. The outcome of mosaic trisomy 16 depends on the cell lines affected.

The impact of cerclage in twin pregnancies on preterm birth rate before 32 weeks

Abstract Purpose: To evaluate whether cerclage in twins reduces the rate of spontaneous preterm birth <32 weeks when compared to expectant management. Methods: This is a retrospective cohort study of twin pregnancies with the following indications for cerclage from two institutions: history of prior preterm birth, ultrasound-identified short cervix ≤2.5u2009cm, and cervical dilation ≥1.0u2009cm. The “cerclage” cohort received a cerclage from a single provider at a single institution from 2003–2016. The “no cerclage” group included all patients with similar indications that were expectantly managed from 2010–2015, at a second institution where cerclages are routinely not performed in twin pregnancies. The primary outcome was the rate of spontaneous preterm birth at <32 weeks. Secondary outcomes were the rates of spontaneous and overall (including medically indicated) preterm births at <32 weeks, <u200934 weeks, and <36 weeks, chorioamnionitis, birth weight, and neonatal mortality within 30 days of life. We also performed a planned subgroup analysis stratified by cerclage indication. Results: In all, 135 women were included in two cohorts: cerclage (nu2009=u200996) or no cerclage (nu2009=u200939). The rates of spontaneous preterm birth <32 weeks were 10.4% (nu2009=u200910) with cerclage versus 28.2% (nu2009=u200911) without cerclage (OR 0.23, CI 0.08–0.70, pu2009=u2009.017). After adjusting for cerclage indication, clinical history, age, chorionicity, insurance type, race, BMI, in-vitro fertilization, and multifetal reduction, there remained a significant reduction in the cerclage group of spontaneous preterm birth <32 weeks (adjusted odds ratio (aOR) 0.24, CI 0.06–0.90, pu2009=u2009.035), spontaneous preterm birth <36 weeks (aOR 0.34, CI 0.04–0.81, pu2009=u2009.013) as well as in overall preterm birth <32 weeks (aOR 0.31, CI 0.1–0.86, pu2009=u2009.018), and overall preterm birth <36 weeks (aOR 0.37, CI 0.10–0.84, pu2009=u2009.030). When stratified by short cervix or cervical dilation in the cerclage versus no cerclage groups, there was a significant decrease in spontaneous preterm birth <32 weeks in the cerclage group with cervical dilation (11.1 versus 41.2%, pu2009=u2009.01) but not in the cerclage group with short cervix only, even for cervical length <1.5u2009cm. Pregnancy latency was 91 days in the cerclage group versus 57 days in the no cerclage group (pu2009=u2009.001), with a median gestational age at delivery of 35 versus 32 weeks (pu2009=u2009.002). There was no increase in chorioamnionitis in the cerclage group. Furthermore, there was a significant increase in birth weight (median 2278 versus 1665u2009g, pu2009<u2009.001) and decrease in perinatal death <30 days (1.6 versus 12.9%, pu2009=u2009.001). Conclusions: Cerclage in twin pregnancies significantly decreased the rate of spontaneous preterm birth <32 weeks compared to expectant management. However, when stratified by cerclage indication, this decrease in primary outcome only remained significant in the group with cervical dilation.

Visual function in infants with antenatal Zika virus exposure

PURPOSEnTo report the findings of a cross-sectional study of visual function in infants with confirmed or suspected antenatal Zika virus (ZIKV) infection seen at a single referral center in Rio de Janeiro.nnnMETHODSnInfants were examined following the ZIKV outbreak period at Instituto Fernandes Figueira/FIOCRUZ. Visual function was considered abnormal if an infant could not fix and follow a standardized high-contrast target (10xa0cm) by 3-6xa0months of age. Visual function and associations with structural eye abnormalities, central nervous system (CNS) abnormalities, microcephaly, and nystagmus were assessed. Sensitivity and specificity of screening criteria for structural eye abnormalities was assessed.nnnRESULTSnA total of 173 infants met inclusion criteria. Abnormal visual function was found in 52 infants (30.0%) and was significantly associated with eye abnormalities (40/52; ORxa0=xa044.2; 95% CI, 16.6-117.6), CNS abnormalities (50/52; ORxa0=xa064.0; 95% CI, 14.7-277.6), microcephaly (44/52; ORxa0=xa031.5; 95% CI, 12.7-77.8), and nystagmus (26/52; ORxa0=xa0120.0; 95% CI, 15.6-924.5). Using microcephaly as screening criteria for the detection of eye abnormalities provided a sensitivity of 88.9% (95% CI, 76.0-96.3) and specificity of 82.8% (95% CI, 75.1-88.9). Using both abnormal visual function and microcephaly increased sensitivity to 100% (95% CI, 92.1-100.0) and decreased specificity to 80.5% (95% CI, 72.5-86.9).nnnCONCLUSIONSnInfants with suspected antenatal ZIKV infection and reduced visual function should be referred to an ophthalmologist. Visual function assessments are helpful in screening for antenatal ZIKV exposure in resource-limited settings and can identify infants who may benefit from visual habilitation.