Shaping the risk for late-life neurodegenerative disease: A systematic review on prenatal risk factors for Alzheimer's disease-related volumetric brain biomarkers.

Environmental exposures including toxins and nutrition may hamper the developing brain in utero, limiting the brain's reserve capacity and increasing the risk for Alzheimer's disease (AD). The purpose of this systematic review is to summarize all currently available evidence for the association between prenatal exposures and AD-related volumetric brain biomarkers. We systematically searched MEDLINE and Embase for studies in humans reporting on associations between prenatal exposure(s) and AD-related volumetric brain biomarkers, including whole brain volume (WBV), hippocampal volume (HV) and/or temporal lobe volume (TLV) measured with structural magnetic resonance imaging (PROSPERO; CRD42020169317). Risk of bias was assessed using the Newcastle Ottawa Scale. We identified 79 eligible studies (search date: August 30th, 2020; Ntotal=24,784; median age 10.7 years) reporting on WBV (N = 38), HV (N = 63) and/or TLV (N = 5) in exposure categories alcohol (N = 30), smoking (N = 7), illicit drugs (N = 14), mental health problems (N = 7), diet (N = 8), disease, treatment and physiology (N = 10), infections (N = 6) and environmental exposures (N = 3). Overall risk of bias was low. Prenatal exposure to alcohol, opioids, cocaine, nutrient shortage, placental dysfunction and maternal anemia was associated with smaller brain volumes. We conclude that the prenatal environment is important in shaping the risk for late-life neurodegenerative disease.

Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study.

BACKGROUND: Similar to other young people with a chronic health condition, perinatally HIV-infected (PHIV) adolescents may have an impacted sexual development. OBJECTIVES: This paper aims to compare sexual milestones of PHIV to HIV uninfected peers, through a systematic review (SR) and explorative study. METHODS: We performed a systematic search in 4 electronic databases (Medline, Embase, Web of Science, and Scopus), according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Last search in all databases was performed in May 2021. We included studies that reported on quantitative data of any of the main outcomes and compared PHIV to HIV uninfected control groups. Main outcomes were defined as the occurrence and/or debut age of sexual milestones (falling in love, having been in a romantic relationship, masturbation, kissing, non-genital caressing (feeling or petting, touching), genital caressing (fingering, handjob), giving or receiving oral sex, and penetrative sex (vaginal or anal). We excluded case reports, audits, guidelines, editorials, abstracts, studies that reported on behaviorally infected HIV patients, studies that did not include an HIV uninfected control group and studies that could not be translated to English or Dutch. We used the Agency for Health Care Research and Quality (AHRQ) Checklist for quality assessment. We performed qualitative synthesis of the data. In the explorative study, we compared sexual milestones of PHIV and HIV uninfected controls matched for age, sex, ethnicity and educational level, using a subset of questions of a validated questionnaire. RESULTS: We included eighteen studies in the SR, describing outcomes of an estimated 1,963 participants. Seventeen studies compared the occurrence and/or debut age of intercourse in PHIV and HIV uninfected controls and 4 studies reported on any of the other sexual milestones. The majority of studies found no difference in occurrence (12 of 16 studies) or debut age (6 of 8 studies) of intercourse in PHIV compared to controls. Two of 4 studies reporting on any of the other milestones found no significant differences between PHIV and HIV uninfected controls. In the explorative study, we included ten PHIV participants and 16 HIV uninfected, matched controls. PHIV tended to report a later debut age of sexual milestones than controls (not significant). STRENGTHS AND LIMITATIONS: The SR includes only a small number of studies and few studies report on non-penetrative milestones. The explorative study adds to this review by including non-penetrative milestones and comparing PHIV to HIV-uninfected, well-matched controls. However, the sample size was small. CONCLUSION: PHIV seem to engage in sexual activities and achieve sexual milestones at a similar rate as their HIV uninfected peers, with a tendency of a later start in well treated PHIV. The review was registered in the PROSPERO database (CRD42021252103) and funded by AIDSfonds. AIDSfonds had no role in the study design or interpretations of this study. ter Haar AM, Fieten A, Van den Hof M, et al. Sexual Development in Perinatally HIV-Infected Young People: A Systematic Review and Explorative Study. Sex Med 2022;10:100578.

Health-related quality of life of perinatally HIV-infected young people: a longitudinal study.

Young people perinatally infected with HIV (pHIV) are at risk of a lowered health-related quality of life (HRQOL). Previous evaluation of the NeurOlogical, VIsual and Cognitive performance in HIV-infected Children (NOVICE)-cohort showed no difference in HRQOL between pHIV and matched HIV-uninfected controls (HIV-), yet a higher percentage of pHIV had impaired HRQOL. The aim of this study is to compare the change over time in HRQOL of pHIV to HIV- over a 5-year period. We used the Pediatric Quality of Life Inventory (PedsQL)™ 4.0 to repeat HRQOL assessment. High PedsQL scores indicate good HRQOL. Fifteen/33 (45.5%) pHIV and 17/37 (45.9%) HIV- completed both assessments. At the first assessment, the mean age was 13.1 years (range 8.0-18.4). PHIV scored higher than HIV- on Emotional functioning and on Total scale score. After five years, the mean age was 17.6 years (range 12.1-22.8). PHIV scored higher than HIV- on all scales, except Social functioning. PHIV did not differ significantly from the Dutch norm on either time-point. LMEM showed no difference in change over time for any of the PedsQL scales. In this study, young people with pHIV receiving high-quality health care, including monitoring of HRQOL, remain to experience a good HRQOL.

Fatigue in children and adolescents perinatally infected with human immunodeficiency virus: an observational study.

BACKGROUND: Fatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL. METHODS: We measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL. RESULTS: We enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2-11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score. CONCLUSIONS: The results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children's HRQOL. Further research should confirm these exploratory findings.

Lower IQ and poorer cognitive profiles in treated perinatally HIV-infected children is irrespective of having a background of international adoption.

BACKGROUND: HIV-associated cognitive deficiency in perinatally HIV-infected (PHIV) children has been studied in Western countries in a population of which an increasing proportion has been internationally adopted. Studies often lack an appropriate internationally adopted HIV-uninfected control group, potentially confounding the relationship between HIV and cognitive functioning. This study aims to further elucidate the association between treated HIV infection and cognitive development by addressing the background of international adoption. METHODS: We cross-sectionally studied the impact of HIV on cognition by comparing PHIV children and HIV- uninfected controls, matched for age-, sex-, ethnicity-, socioeconomic status (SES)- and adoption status. We used a standardized neuropsychological test battery to measure intelligence (IQ), and the cognitive domains of processing speed, working memory, executive function, learning ability and visual-motor function and compared outcomes using lineair regression models, adjusted for IQ. We determined cognitive profiles and cognitive impairment by using multivariate normative comparison (MNC) and explored associations with HIV disease- and treatment-related factors. RESULTS: We enrolled fourteen PHIV children (mean age 10.45 years [1.73 SD], 93% adopted from sub-Saharan Africa at a median age of 3.3 years [IQR 2.1-4.2]) and fifteen HIV- uninfected controls. Groups did not clinically nor statistically differ in age, sex, ethnicity, SES, region of birth, adoption status and age at adoption. PHIV scored consistently lower on all cognitive domains and MNC outcomes. Compared to controls, PHIV children had a significant lower IQ (mean 81 [SD 11] versus mean 97 [SD 15], p = 0.005), and a poorer cognitive profile by MNC (Hotelling's T2 mean -4.36 [SD 5.6] versus mean 0.16 [SD 4.5], p = 0.021), not associated with HIV disease- and treatment-related factors. Two PHIV (14%) and one control (7%) were classified as cognitively impaired (p = 0.598). CONCLUSIONS: Findings indicate treated HIV-infection to be independently associated with lower IQ and poorer cognitive profiles in PHIV children, irrespective of a background of international adoption.

Severe laryngeal stenosis in newly born twins with 22q11.2 deletion syndrome: A case report.

Chromosome 22q11.2 deletion syndrome is common and presents with a range of clinical features from cardiac malformations to hypocalcemia. Laryngeal anomalies are not a common feature of this syndrome. We describe newly born twins who presented with unexpected severe birth depression secondary to severe type IV glottic webs requiring extensive resuscitation and emergency tracheostomy. They were diagnosed postnatally to have deletion of 22q11.2. The successful resuscitation of these infants at birth was only possible because they were born in a tertiary care hospital. This report shows the critical nature of prenatal diagnosis of 22q11.2 deletion syndrome.

Maternal complications with placenta previa.

The purpose of this study is to describe the maternal complications of placenta previa. A population-based retrospective cohort study including all women delivered in the province of Nova Scotia, Canada from 1988 to 1995 was performed. Patient information was obtained from the Nova Scotia Atlee Perinatal Database and maternal complications were described for all women undergoing cesarean delivery. Prognostic factors for the risk of hysterectomy in woman with placenta previa were analyzed by multiple logistic regression. During the 8-year period, 308 cases of placenta previa were identified in 93,996 deliveries (0.33%). Maternal complications included hysterectomy [relative risk (RR) = 33.26], antepartum bleeding (RR = 9.81), intrapartum (RR = 2.48), and postpartum (RR = 1.86) hemorrhages, as well as blood transfusion (RR = 10.05), septicemia (RR = 5.55), and thrombophlebitis (RR = 4.85). Risk factors for need of hysterectomy in women with placenta previa include the presence of placenta accreta and previous cesarean delivery.

Neonatal outcomes with placenta previa.

OBJECTIVE: To identify neonatal complications associated with placenta previa. METHODS: This was a population-based, retrospective cohort study involving all singleton deliveries in Nova Scotia from 1988 to 1995. The study group consisted of all completed singleton pregnancies complicated by placenta previa; all other singleton pregnancies were considered controls. Patient information was collected from the Nova Scotia Atlee perinatal database. Neonatal complications were evaluated while controlling for potential confounders. The data were analyzed using chi2, Fisher exact test, and multiple logistic regression. RESULTS: Among 92,983 pregnancies delivered during the study period, 305 cases of placenta previa were identified (0.33%). After controlling for potential confounders, neonatal complications significantly associated with placenta previa included major congenital anomalies (odds ratio [OR] 2.48), respiratory distress syndrome (OR 4.94), and anemia (OR 2.65). The perinatal mortality rate associated with placenta previa was 2.30% (compared with 0.78% in controls) and was explained by gestational age at delivery, occurrence of congenital anomalies, and maternal age. Although there was a higher rate of preterm births in the placenta previa group (46.56% versus 7.27%), there was no difference in birth weights between groups after controlling for gestational age at delivery. CONCLUSION: Neonatal complications of placenta previa included preterm birth, congenital anomalies, respiratory distress syndrome, and anemia. There was no increased occurrence of fetal growth restriction.

Semi-Fowler's positioning, lateral tilts, and their effects on nonstress tests.

OBJECTIVE: To determine whether a lateral tilt for women in semi-Fowler's position for antepartum nonstress tests (NSTs) (a) promotes NST reactivity or (b) shortens testing time required to obtain a reactive tracing. SETTING: An antepartum fetal assessment unit of a tertiary care facility in eastern Canada. DESIGN: In this prospective, randomized study, a computer analysis of the NSTs was used to obtain an objective, standardized interpretation of fetal heart rate reactivity. Participants were randomly assigned to two experimental groups using semi-Fowler's position with a 45-degree tilt to either the left or right, or to a control group using semi-Fowler's position with no lateral tilt. PARTICIPANTS: A convenience sample of 823 nonstress tests was obtained from women with singleton pregnancies, intact amniotic membranes, and gestations between 32 and 42 weeks. The final sample available for analysis totaled 738 nonstress tests from 573 pregnancies. MAIN OUTCOME MEASURES: Percentage of reactive nonstress tests and the number of minutes required for tests to be reactive. RESULTS: The rate of reactive NSTs and the time to achieve a reactive NST did not differ statistically for any of the three study groups. Likewise, NST outcomes were similar when the left-tilt group was compared with the right-tilt group. Although no significant differences were found between study groups, less than 2% of the women in the control group (semi-Fowler's position without a lateral tilt) experienced symptoms consistent with supine hypotensive syndrome. CONCLUSIONS: No statistically or clinically significant differences were found in nonstress tests between the three groups. Lateral tilting did not shorten test time. Results do suggest that hemodynamic changes can occur in 3rd trimester women who are in semi-Fowler's position without a lateral tilt. Lateral tilting of gravidas in semi-Fowler's position during nonstress testing is thus supported to avoid hypotensive symptoms.

Transvaginal ultrasound in the prediction of preterm delivery: singleton and twin gestations.

OBJECTIVE: To compare, in singleton and twin pregnancies, the effectiveness of transvaginal ultrasound versus digital examination in predicting preterm delivery in women with suspected preterm labor. METHODS: Transvaginal ultrasound and pelvic examinations were performed on patients admitted with suspected preterm labor between 23 and 33 weeks' gestation. Ultrasound assessment of cervical length and the presence of funneling with fundal pressure were recorded for each patient, and the results were compared with dilatation and effacement as assessed by digital examination for the prediction of preterm delivery in the two groups (singletons and twins). RESULTS: One hundred sixty-two subjects were recruited (136 singletons and 26 twin pregnancies), with no significant demographic differences between the groups. Overall, 33% of the participants delivered preterm (27% of singletons, 62% of twins). Using receiver operating characteristics curves, the best cutoff points were 30 mm for endocervical length at ultrasound, 50% for effacement, and 1.5 cm for dilatation. Of these, the best predictor was endocervical length, which was a better predictor in singleton than in twin pregnancies. Of the potential predictors, including endocervical length, funneling, dilatation, and effacement, only endocervical length was an independent predictor of preterm delivery at less than 34 weeks' gestation for both singletons and twins by multiple logistic regression. When analyzed for delivery at less than 37 weeks' gestation, this relation held true for singletons but not twins. Endocervical length less than 30 mm had a sensitivity of 81% and 75%, specificity of 65% and 30%, positive predictive value of 46% and 63%, and negative predictive value of 90% and 43% for singleton and twin pregnancies, respectively, in predicting spontaneous birth at less than 37 weeks' gestation. CONCLUSION: Between 23 and 33 weeks' gestation, transvaginal ultrasound assessment of endocervical length is superior to funneling and digital examination in predicting preterm delivery in patients who present with suspected preterm labor, and is a better predictor in singletons than in twins.

What has happened to Prägnanz? Coding, stability, or resonance.

Three theoretical measures of Prägnanz were compared with four data sets. The theoretical measures were a stimulus-coding one (structural information load, SIL), a measure related to within memory processes (stability), and one based on the interaction of perception and memory (resonance). The four data sets were obtained in two experiments and involved goodness rating, grouping, and immediate and delayed recall. A complete set of seven-element binary serial patterns was used in each experiment. Both SIL and resonance were shown to correlate reliably with the data sets across tasks. The resonance measure, however, performed best. Prägnanz thus appears to be explained better by resonance than by stimulus coding or memory storage. Resonance explained all systematic variance in the recall tasks, but not in the other tasks. Regarding these, partial-correlation analyses showed that the effect of stability could be fully reduced to resonance. SIL could not be similarly reduced. Therefore, additional perceptual constraints, other than resonance, would be needed for a complete account of goodness in the judging or grouping tasks.

Uterine artery Doppler in the investigation of pregnancies with raised maternal serum alpha-fetoprotein.

Uterine artery flow velocity waveforms (FVW) were obtained prospectively by continuous wave Doppler at 18-22 weeks gestation from 98 women with an unexplained elevation in maternal serum alpha-fetoprotein (MSAFP). A notch in either the left or right uterine artery FVW was present in 18 pregnancies of which seven resulted in perinatal death and six in the birth of very immature and/or severely growth retarded babies. Conversely, in 66 of 80 pregnancies the absence of a notch was associated with the livebirth of an infant beyond 32 weeks gestation, with a birthweight above the 5th centile. It is suggested that the presence of a notch in the uterine artery FVW is a good predictor of poor perinatal outcome.

Platelet count in normal, small, and anemic fetuses.

A reference range for fetal platelet count with gestation was established from the study of samples obtained by cordocentesis from 229 pregnancies that had prenatal diagnosis. The mean platelet count increased from 187 +/- 47 x 10(9)/L at 15 weeks to 274 +/- 47 x 10(9)/L at 40 weeks' gestation. In 113 red cell-isoimmunized pregnancies, the moderately anemic fetuses were significantly thrombocythenic, whereas the severely anemic fetuses were thrombocytopenic. In 136 small-for-gestational-age fetuses the platelet count was reduced and there were significant correlations between the magnitude of the thrombocytopenia and the degree of fetal smallness, hypoxemia, and acidemia.

Evaluation of the lemon and banana signs in one hundred thirty fetuses with open spina bifida.

The incidence and diagnostic accuracy of the lemon and cerebellar ultrasonographic markers, as well as head size and ventriculomegaly, were evaluated in a study of 1561 patients at high risk for fetal neural tube defects. In the 130 fetuses with open spina bifida there was a relationship between gestational age and the presence of each of these markers. The lemon sign was present in 98% of fetuses at less than or equal to 24 weeks' gestation but in only 13% of those at greater than 24 weeks' gestation. Cerebellar abnormalities were present in 95% of fetuses irrespective of gestation; however, the cerebellar abnormality at less than or equal to 24 weeks' gestation was predominantly the banana sign (72%) whereas at gestations greater than 24 weeks it was cerebellar "absence" (81%). Both growth retardation and cerebral ventriculomegaly significantly worsened with gestation while the head circumference remained disproportionately small throughout gestation. On the basis of these data, a new approach is proposed for the investigation of patients at high risk for fetal open spina bifida.

Mean red cell volume in normal, anemic, small, trisomic and triploid fetuses.

A reference range for fetal mean red cell volume (MCV) with gestation was established from the study of samples obtained by cordocentesis from 466 pregnancies undergoing prenatal diagnosis for non-erythrocyte abnormalities. The mean MCV decreased from 145 fl at 16 weeks to 113 fl at 36 weeks of gestation. Alterations in MCV were investigated in 154 red cell isoimmunized and 231 small for gestational age (SGA) fetuses. In red cell isoimmunization, significant macrocytosis was observed when the fetal hemoglobin concentration deficit was greater than or equal to 6 g/dl. In the chromosomally normal SGA fetuses (n = 178), the MCV was increased and the magnitude of macrocytosis was significantly associated with gestation and the degrees of fetal 'smallness' and fetal hypoxemia. However, the most severely macrocytotic SGA fetuses were those with triploidy (n = 22). In the SGA fetuses with other chromosomal defects (n = 31), the MCV was higher than the controls but lower than that of the chromosomally normal hypoxemic fetuses. It is suggested that in severe growth retardation there is developmental delay in the normal evolution from hepatic to medullary hemopoiesis and this is most marked in triploid fetuses. In contrast, in red cell isoimmunization the switch to medullary erythropoiesis is normal, but in severe anemia there is secondary recruitment of hepatic erythropoiesis.