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Concept: Fetus

867

A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.

Concepts: Pregnancy, Embryo, Fetus, Uterus, Infection, Cerebral cortex, Cerebellum, Gestational age

783

Background Zika virus (ZIKV) has been linked to neonatal microcephaly. To characterize the spectrum of ZIKV disease in pregnancy, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in fetuses. Methods We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed the women prospectively and collected clinical and ultrasonographic data. Results A total of 88 women were enrolled from September 2015 through February 2016; of these 88 women, 72 (82%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 5 to 38 weeks of gestation. Predominant clinical features included pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 28% had fever (short-term and low-grade). Women who were positive for ZIKV were more likely than those who were negative for the virus to have maculopapular rash (44% vs. 12%, P=0.02), conjunctival involvement (58% vs. 13%, P=0.002), and lymphadenopathy (40% vs. 7%, P=0.02). Fetal ultrasonography was performed in 42 ZIKV-positive women (58%) and in all ZIKV-negative women. Fetal abnormalities were detected by Doppler ultrasonography in 12 of the 42 ZIKV-positive women (29%) and in none of the 16 ZIKV-negative women. Adverse findings included fetal deaths at 36 and 38 weeks of gestation (2 fetuses), in utero growth restriction with or without microcephaly (5 fetuses), ventricular calcifications or other central nervous system (CNS) lesions (7 fetuses), and abnormal amniotic fluid volume or cerebral or umbilical artery flow (7 fetuses). To date, 8 of the 42 women in whom fetal ultrasonography was performed have delivered their babies, and the ultrasonographic findings have been confirmed. Conclusions Despite mild clinical symptoms, ZIKV infection during pregnancy appears to be associated with grave outcomes, including fetal death, placental insufficiency, fetal growth restriction, and CNS injury.

Concepts: Pregnancy, Embryo, Fetus, Uterus, Obstetrics, Medical ultrasonography, Gestational age, Amniotic fluid

453

This study compared fetal response to musical stimuli applied intravaginally (intravaginal music [IVM]) with application via emitters placed on the mother’s abdomen (abdominal music [ABM]). Responses were quantified by recording facial movements identified on 3D/4D ultrasound. One hundred and six normal pregnancies between 14 and 39 weeks of gestation were randomized to 3D/4D ultrasound with: (a) ABM with standard headphones (flute monody at 98.6 dB); (b) IVM with a specially designed device emitting the same monody at 53.7 dB; or © intravaginal vibration (IVV; 125 Hz) at 68 dB with the same device. Facial movements were quantified at baseline, during stimulation, and for 5 minutes after stimulation was discontinued. In fetuses at a gestational age of >16 weeks, IVM-elicited mouthing (MT) and tongue expulsion (TE) in 86.7% and 46.6% of fetuses, respectively, with significant differences when compared with ABM and IVV (p = 0.002 and p = 0.004, respectively). There were no changes from baseline in ABM and IVV. TE occurred ≥5 times in 5 minutes in 13.3% with IVM. IVM was related with higher occurrence of MT (odds ratio = 10.980; 95% confidence interval = 3.105-47.546) and TE (odds ratio = 10.943; 95% confidence interval = 2.568-77.037). The frequency of TE with IVM increased significantly with gestational age (p = 0.024). Fetuses at 16-39 weeks of gestation respond to intravaginally emitted music with repetitive MT and TE movements not observed with ABM or IVV. Our findings suggest that neural pathways participating in the auditory-motor system are developed as early as gestational week 16. These findings might contribute to diagnostic methods for prenatal hearing screening, and research into fetal neurological stimulation.

Concepts: Pregnancy, Embryo, Prenatal development, Fetus, Uterus, Obstetrics, Gestation, Gestational age

435

Zika virus is a cause of microcephaly and brain abnormalities (1), and it is the first known mosquito-borne infection to cause congenital anomalies in humans. The establishment of a comprehensive surveillance system to monitor pregnant women with Zika virus infection will provide data to further elucidate the full range of potential outcomes for fetuses and infants of mothers with asymptomatic and symptomatic Zika virus infection during pregnancy. In February 2016, Zika virus disease and congenital Zika virus infections became nationally notifiable conditions in the United States (2). Cases in pregnant women with laboratory evidence of Zika virus infection who have either 1) symptomatic infection or 2) asymptomatic infection with diagnosed complications of pregnancy can be reported as cases of Zika virus disease to ArboNET* (2), CDC’s national arboviral diseases surveillance system. Under existing interim guidelines from the Council for State and Territorial Epidemiologists (CSTE), asymptomatic Zika virus infections in pregnant women who do not have known pregnancy complications are not reportable. ArboNET does not currently include pregnancy surveillance information (e.g., gestational age or pregnancy exposures) or pregnancy outcomes. To understand the full impact of infection on the fetus and neonate, other systems are needed for reporting and active monitoring of pregnant women with laboratory evidence of possible Zika virus infection during pregnancy. Thus, in collaboration with state, local, tribal, and territorial health departments, CDC established two surveillance systems to monitor pregnancies and congenital outcomes among women with laboratory evidence of Zika virus infection(†) in the United States and territories: 1) the U.S. Zika Pregnancy Registry (USZPR),(§) which monitors pregnant women residing in U.S. states and all U.S. territories except Puerto Rico, and 2) the Zika Active Pregnancy Surveillance System (ZAPSS), which monitors pregnant women residing in Puerto Rico. As of May 12, 2016, the surveillance systems were monitoring 157 and 122 pregnant women with laboratory evidence of possible Zika virus infection from participating U.S. states and territories, respectively. Tracking and monitoring clinical presentation of Zika virus infection, all prenatal testing, and adverse consequences of Zika virus infection during pregnancy are critical to better characterize the risk for congenital infection, the performance of prenatal diagnostic testing, and the spectrum of adverse congenital outcomes. These data will improve clinical guidance, inform counseling messages for pregnant women, and facilitate planning for clinical and public health services for affected families.

Concepts: Pregnancy, Embryo, Fetus, United States, Obstetrics, U.S. state, Gestational age, Territories of the United States

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In early 2015, an outbreak of Zika virus, a flavivirus transmitted by Aedes mosquitoes, was identified in northeast Brazil, an area where dengue virus was also circulating. By September, reports of an increase in the number of infants born with microcephaly in Zika virus-affected areas began to emerge, and Zika virus RNA was identified in the amniotic fluid of two women whose fetuses had been found to have microcephaly by prenatal ultrasound. The Brazil Ministry of Health (MoH) established a task force to investigate the possible association of microcephaly with Zika virus infection during pregnancy and a registry for incident microcephaly cases (head circumference ≥2 standard deviations [SD] below the mean for sex and gestational age at birth) and pregnancy outcomes among women suspected to have had Zika virus infection during pregnancy. Among a cohort of 35 infants with microcephaly born during August-October 2015 in eight of Brazil’s 26 states and reported to the registry, the mothers of all 35 had lived in or visited Zika virus-affected areas during pregnancy, 25 (71%) infants had severe microcephaly (head circumference >3 SD below the mean for sex and gestational age), 17 (49%) had at least one neurologic abnormality, and among 27 infants who had neuroimaging studies, all had abnormalities. Tests for other congenital infections were negative. All infants had a lumbar puncture as part of the evaluation and cerebrospinal fluid (CSF) samples were sent to a reference laboratory in Brazil for Zika virus testing; results are not yet available. Further studies are needed to confirm the association of microcephaly with Zika virus infection during pregnancy and to understand any other adverse pregnancy outcomes associated with Zika virus infection. Pregnant women in Zika virus-affected areas should protect themselves from mosquito bites by using air conditioning, screens, or nets when indoors, wearing long sleeves and pants, using permethrin-treated clothing and gear, and using insect repellents when outdoors. Pregnant and lactating women can use all U.S. Environmental Protection Agency (EPA)-registered insect repellents according to the product label.

Concepts: Pregnancy, Childbirth, Embryo, Fetus, Mosquito, Obstetrics, Dengue fever, Gestational age

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In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants.

Concepts: Pregnancy, Childbirth, Infant, Fetus, Breastfeeding, Centers for Disease Control and Prevention

259

Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation.

Concepts: Vitamin D, Pregnancy, Childbirth, Fetus, Randomized controlled trial, Breastfeeding

194

A 30-year-old woman presented with an uncomplicated pregnancy until ultrasonography at 19 weeks revealed severe oligohydramnios and a fetus that appeared to be extrauterine. Imaging confirmed an abdominal ectopic pregnancy, with no uterine wall visible surrounding the fetus.

Concepts: Pregnancy, Childbirth, Embryo, Fetus, Uterus, Obstetrics, Ectopic pregnancy, Oligohydramnios

185

Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts.

Concepts: Pregnancy, Childbirth, Infant, Fetus, Obstetrics, Gestational age, Pharmacoeconomics, Global health

179

To investigate if the lack of gestational age correction may explain some of the school failure seen in ex-preterm infants.

Concepts: Pregnancy, Childbirth, Fetus, Gestational age