Maternal PlGF and umbilical Dopplers predict pregnancy outcomes at diagnosis of early-onset fetal growth restriction.

BACKGROUNDSevere, early-onset fetal growth restriction (FGR) causes significant fetal and neonatal mortality and morbidity. Predicting the outcome of affected pregnancies at the time of diagnosis is difficult, thus preventing accurate patient counseling. We investigated the use of maternal serum protein and ultrasound measurements at diagnosis to predict fetal or neonatal death and 3 secondary outcomes: fetal death or delivery at or before 28+0 weeks, development of abnormal umbilical artery (UmA) Doppler velocimetry, and slow fetal growth.METHODSWomen with singleton pregnancies (n = 142, estimated fetal weights [EFWs] below the third centile, less than 600 g, 20+0 to 26+6 weeks of gestation, no known chromosomal, genetic, or major structural abnormalities) were recruited from 4 European centers. Maternal serum from the discovery set (n = 63) was analyzed for 7 proteins linked to angiogenesis, 90 additional proteins associated with cardiovascular disease, and 5 proteins identified through pooled liquid chromatography and tandem mass spectrometry. Patient and clinician stakeholder priorities were used to select models tested in the validation set (n = 60), with final models calculated from combined data.RESULTSThe most discriminative model for fetal or neonatal death included the EFW z score (Hadlock 3 formula/Marsal chart), gestational age, and UmA Doppler category (AUC, 0.91; 95% CI, 0.86-0.97) but was less well calibrated than the model containing only the EFW z score (Hadlock 3/Marsal). The most discriminative model for fetal death or delivery at or before 28+0 weeks included maternal serum placental growth factor (PlGF) concentration and UmA Doppler category (AUC, 0.89; 95% CI, 0.83-0.94).CONCLUSIONUltrasound measurements and maternal serum PlGF concentration at diagnosis of severe, early-onset FGR predicted pregnancy outcomes of importance to patients and clinicians.TRIAL REGISTRATIONClinicalTrials.gov NCT02097667.FUNDINGThe European Union, Rosetrees Trust, Mitchell Charitable Trust.

Prenatal interventions for fetal growth restriction in animal models: A systematic review.

Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

Birth outcomes between 22 and 26 weeks' gestation in national population-based cohorts from Sweden, England and France.

AIM: We investigated the timing of survival differences and effects on morbidity for foetuses alive at maternal admission to hospital delivered at 22 to 26 weeks' gestational age (GA). METHODS: Data from the EXPRESS (Sweden, 2004-07), EPICure-2 (England, 2006) and EPIPAGE-2 (France, 2011) cohorts were harmonised. Survival, stratified by GA, was analysed to 112 days using Kaplan-Meier analyses and Cox regression adjusted for population and pregnancy characteristics; neonatal morbidities, survival to discharge and follow-up and outcomes at 2-3 years of age were compared. RESULTS: Among 769 EXPRESS, 2310 EPICure-2 and 1359 EPIPAGE-2 foetuses, 112-day survival was, respectively, 28.2%, 10.8% and 0.5% at 22-23 weeks' GA; 68.5%, 40.0% and 23.6% at 24 weeks; 80.5%, 64.8% and 56.9% at 25 weeks; and 86.6%, 77.1% and 74.4% at 26 weeks. Deaths were most marked in EPIPAGE-2 before 1 day at 22-23 and 24 weeks GA. At 25 weeks, survival varied before 28 days; differences at 26 weeks were minimal. Cox analyses were consistent with the Kaplan-Meier analyses. Variations in morbidities were not clearly associated with survival. CONCLUSION: Differences in survival and morbidity outcomes for extremely preterm births are evident despite adjustment for background characteristics. No clear relationship was identified between early mortality and later patterns of morbidity.

Detection and clinical outcome of small-for-gestational-age fetuses in the third trimester-A comparison between routine ultrasound examination and examination on indication.

INTRODUCTION: Fetal growth restriction is a major risk factor for adverse perinatal outcome. As most of the growth-restricted fetuses are small for gestational age (SGA), an efficient antenatal screening method for SGA fetuses would have a major impact on perinatal health. The aim of this study was to compare the SGA prediction rate achieved with third-trimester routine ultrasound estimation of fetal weight (EFW) with that obtained using ultrasound examination on indication. The secondary aim was to evaluate the clinical outcome in relation to the SGA screening method. MATERIAL AND METHODS: During 1995-2009, two perinatal centers in southern Sweden offered routine ultrasound examination at 32-34 gestational weeks to 99 265 women with singleton pregnancies. Of these, 59 452 (60%) underwent the ultrasound examination. The other population, comprising 24 868 pregnancies, was cared for in another three centers that used a risk-based method with ultrasound examinations on indication only. Of them, 5792 (23%) underwent ultrasound examination at 32-36 gestational weeks. The deviation in the EFW from the expected one was expressed as the EFW z-score, SGA EFW being defined as the EFW z-score less than -2. SGA prediction ability was assessed by receiver operating characteristic (ROC) curves. Crude and adjusted risk ratios were calculated for selected variables of perinatal outcome when comparing the populations. RESULTS: The SGA prediction ability for routine ultrasound was high, area under the ROC curve was 0.90 (95% CI 0.89-0.91). For an EFW z-score of -1, the sensitivity was 67.3% and specificity was 90.5% among routinely screened pregnancies; corresponding numbers in the ultrasound on indication population were 34.3% and 96.6%. The screened population had a lower risk of preterm birth, birthweight z-score less than -3, and Apgar score less than 7 at 5 min with adjusted risk ratios 0.87 (95% CI 0.82-0.92), 0.75 (95% CI 0.61-0.92), and 0.77 (95% CI 0.68-0.87), respectively. No difference in perinatal mortality was detected. There were no differences in perinatal outcome between the two subcohorts of infants born SGA. CONCLUSIONS: Third-trimester routine ultrasound improves the detection of SGA antenatally compared with ultrasound performed on indication, but no convincing improvement in perinatal outcome was identified.

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

Safety Aspects of Perinatal Ultrasound.

Ultrasound safety is of particular importance in fetal and neonatal scanning. Fetal tissues are vulnerable and often still developing, the scanning depth may be low, and potential biological effects have been insufficiently investigated. On the other hand, the clinical benefit may be considerable. The perinatal period is probably less vulnerable than the first and second trimesters of pregnancy, and ultrasound is often a safer alternative to other diagnostic imaging modalities. Here we present step-by-step procedures for obtaining clinically relevant images while maintaining ultrasound safety. We briefly discuss the current status of the field of ultrasound safety, with special attention to the safety of novel modalities, safety considerations when ultrasound is employed for research and education, and ultrasound of particularly vulnerable tissues, such as the neonatal lung. This CME is prepared by ECMUS, the safety committee of EFSUMB, with contributions from OB/GYN clinicians with a special interest in ultrasound safety.

Cerebroplacental ratio as predictor of adverse perinatal outcome in the third trimester.

INTRODUCTION: Fetal growth restriction is associated with adverse perinatal outcome and the clinical management of these pregnancies is a challenge. The aim of this study was to investigate the potential of cerebroplacental ratio (CPR) to predict adverse perinatal outcome in high-risk pregnancies in the third trimester. Another aim was to study whether the CPR has better predictive value than its components, middle cerebral artery (MCA) pulsatility index (PI) and umbilical artery (UA) PI. MATERIAL AND METHODS: The study was a retrospective cohort study including 1573 singleton high-risk pregnancies with Doppler examinations performed at 32+0 to 40+6 gestational weeks at Lund University Hospital and the University Hospital of Malmö between 29 December 1994 and 31 December 2017. Receiver operating characteristics (ROC) curves were used to investigate the predictive value of the gestational age-specific z-scores for CPR, UA PI and MCA PI, respectively, for the primary outcome "perinatal asphyxia/mortality" and the secondary outcomes "birthweight small for gestational age (SGA)" and two composite outcomes: "appropriate for gestational age/large for gestational age liveborn infants with neonatal morbidity" and "SGA liveborn infants with neonatal morbidity." RESULTS: The performance in predicting perinatal asphyxia/mortality was poor for all three variables and did not differ significantly. The ROC area under curve (AUC) was 0.56, 0.55 and 0.53 for CPR, UA PI and MCA PI z-scores, respectively. The ROC AUC for CPR z-scores to predict SGA was 0.73, significantly higher than that for either UA PI or MCA PI (P < .001). The ability of CPR and the MCA PI to predict appropriate for gestational age/large for gestational age infant morbidity and SGA infant morbidity was similar and significantly better than UA PI (P < .001). CONCLUSIONS: In the present study, none of the three Doppler measures proved to be useful in predicting perinatal asphyxia and mortality. CPR and MCA PI were equally good in predicting neonatal morbidity, especially in SGA pregnancies, and both were significantly better predictors than the UA PI. CPR had a high predictive value for SGA at birth, better than that of its two components, UA PI and MCA PI.

Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5 years.

AIM: It is not clear whether perinatal acidosis can predict poor outcomes in extremely preterm infants and we investigated associations between intrapartum hypoxia and mortality and neurodevelopmental outcomes. METHODS: We used nationwide data on 705 infants from the Extremely Preterm Infants in Sweden Study, delivered at 22-26 weeks of gestation during 2004-2007. Comprehensive neurodevelopmental assessments were performed on survivors at 2.5 (n = 456) and 6.5 (n = 441) years of corrected age. Gestational age-related changes in umbilical cord arterial pH were compared with reference values for term newborn infants, and base excess was also calculated. Associations between low blood gas values (<10th percentile) and mortality and neurodevelopmental outcome were estimated. RESULTS: Cord blood determination was more common in surviving infants (P < .001), with pH determined in 322/705 (46%) and base excess in 311/705 (44%). Extremely preterm infants had higher pH values than term infants (P < .0001), with no change from 22 to 26 weeks of gestation (P = .61, r2  = .001). Multiple logistic regression showed no association between low blood gas values and risk of death or neurodevelopmental impairment at 6.5 years (P ≥ .17). CONCLUSION: Hypoxia with acidosis at birth was not associated with an increased risk of death or impaired neurodevelopmental in extremely preterm born children at 6.5 years.

Association Between Year of Birth and 1-Year Survival Among Extremely Preterm Infants in Sweden During 2004-2007 and 2014-2016.

Importance: Since 2004-2007, national guidelines and recommendations have been developed for the management of extremely preterm births in Sweden. If and how more uniform management has affected infant survival is unknown. Objective: To compare survival of extremely preterm infants born during 2004-2007 with survival of infants born during 2014-2016. Design, Setting and Participants: All births at 22-26 weeks' gestational age (n = 2205) between April 1, 2004, and March 31, 2007, and between January 1, 2014, and December 31, 2016, in Sweden were studied. Prospective data collection was used during 2004-2007. Data were obtained from the Swedish pregnancy, medical birth, and neonatal quality registries during 2014-2016. Exposures: Delivery at 22-26 weeks' gestational age. Main Outcomes and Measures: The primary outcome was infant survival to the age of 1 year. The secondary outcome was 1-year survival among live-born infants who did not have any major neonatal morbidity (specifically, without intraventricular hemorrhage grade 3-4, cystic periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity stage 3-5, or severe bronchopulmonary dysplasia). Results: During 2004-2007, 1009 births (3.3/1000 of all births) occurred at 22-26 weeks' gestational age compared with 1196 births (3.4/1000 of all births) during 2014-2016 (P = .61). One-year survival among live-born infants at 22-26 weeks' gestational age was significantly lower during 2004-2007 (497 of 705 infants [70%]) than during 2014-2016 (711 of 923 infants [77%]) (difference, -7% [95% CI, -11% to -2.2%], P = .003). One-year survival among live-born infants at 22-26 weeks' gestational age and without any major neonatal morbidity was significantly lower during 2004-2007 (226 of 705 infants [32%]) than during 2014-2016 (355 of 923 infants [38%]) (difference, -6% [95% CI, -11% to -1.7%], P = .008). Conclusions and Relevance: Among live births at 22-26 weeks' gestational age in Sweden, 1-year survival improved between 2004-2007 and 2014-2016.

Brain Volumes and Developmental Outcome in Childhood Following Fetal Growth Restriction Leading to Very Preterm Birth.

Background: Children born very preterm (PT) after fetal growth restriction (FGR) exhibit cognitive impairment at early school age. The relationship between neurodevelopmental impairment and attained regional brain volumes is unknown. Methods: We studied 23 preterm children with FGR (PT-FGR), 24 matched preterm children AGA (PT-AGA), and 27 matched term AGA children (T-AGA) by measuring brain volumes with magnetic resonance imaging at early school age. Cognitive and motor functions were assessed by the Wechsler Intelligence Scales for Children and the ABC-Movement score. Results: The mean (SD) full-scale IQ was 80 (17) in the PT-FGR group and 103 (12) in the PT-AGA group (p < 0.001). The PT-FGR group had lower mean total, gray matter, white matter, thalamic, cerebellar white matter, and hippocampal volumes as compared to the T-AGA group (p = 0.01, 0.04, 0.003, 0.002, 0.001, and 0.009, respectively). Brain volumes did not differ significantly between the PT groups. Reduction of hippocampal volume correlated with degree of growth restriction at birth (r = 0.46, p = 0.05). Neither the full-scale IQ nor the ABC movement score <5th percentile were related to brain volumes. Conclusion: Brain volumes as determined by MRI at early school age were primarily associated with degree of prematurity at birth and less with FGR. Regional brain volumes did not discriminate cognitive and motor function beyond that predicted by gestational age at birth.

Reduced Prevalence of Severe Intraventricular Hemorrhage in Very Preterm Infants Delivered after Maternal Preeclampsia.

BACKGROUND: Very preterm (VPT) delivery after severe preeclampsia (PE) has been associated with adverse perinatal outcome. It is unclear whether fetal exposure to PE per se modifies the prevalence of neonatal morbidities associated with VPT birth. OBJECTIVES: To evaluate neonatal morbidity in VPT infants exposed to maternal PE compared to morbidity in nonexposed VPT infants. METHODS: This retrospective study consisted of all inborn infants delivered before 30 gestational weeks admitted to a tertiary-level neonatal intensive care unit between 1998 and 2014: 195 infants exposed to maternal PE were compared to 957 infants without maternal PE (background group). Prevalence rates of neonatal morbidity, cerebral palsy (CP), and mortality at 2 years of age were obtained from patient records. RESULTS: The PE group had a lower median (IQR) birth weight (795 [262] g) and a higher median gestational age (GA) (27 [3] weeks) at birth than the background group (890 [385] g and 26 [3] weeks, respectively; both p < 0.001). Exposure to maternal PE was associated with lower rates of severe intraventricular hemorrhage (IVH) (2 vs. 11%), retinopathy of prematurity requiring treatment (2 vs. 7%), mortality (9 vs. 15%), and CP (4 vs. 8%). Exposure to PE remained associated with a reduced prevalence of severe IVH (OR 0.17, 95% CI 0.05-0.57) after adjustment for GA, multiple birth, Apgar score, delivery mode, sex, and antenatal steroid treatment. CONCLUSION: Fetal exposure to PE is associated with a decreased rate of severe IVH following VPT birth. Studies on underlying mechanisms may provide a basis for prevention of IVH in the VPT infant.

Physiological adaptation of the growth-restricted fetus.

The growth-restricted fetus in utero is exposed to a hostile environment and suffers undernutrition and hypoxia. To cope with the stress, the fetus changes its physiological functions. These adaptive changes aid intrauterine survival; however, they can lead to permanent functional and structural changes that can contribute to the development of serious chronic diseases later in life. Epigenetic mechanisms are an important part of the pathophysiological processes behind this "developmental origin of adult diseases." The dominant cardiovascular adaptive change is the redistribution of blood flow in hypoxic fetuses, with preferential supply of blood to the fetal brain, myocardium, and adrenal glands. The proportion of blood from the umbilical vein to the ductus venosus and foramen ovale increases, which increases the cardiac output of the left heart ventricle. The increased perfusion of fetal brain can be followed with Doppler ultrasound as increased diastolic velocities and decreased pulsatility index in the middle cerebral artery.

Outcome of extremely preterm infants after iatrogenic or spontaneous birth.

INTRODUCTION: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. MATERIAL AND METHODS: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. RESULTS: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. CONCLUSIONS: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.

Antenatal corticosteroids: a retrospective cohort study on timing, indications and neonatal outcome.

INTRODUCTION: An antenatal corticosteroid (ACS) delivery interval of 24 h to seven days is commonly referred to as optimal timing. We aimed to investigate whether the ACS delivery interval was associated with the obstetric indication for treatment and with neonatal complications. MATERIAL AND METHODS: The study was a retrospective chart review of clinical data from preterm neonates delivered at the Skåne University Hospital, Lund University, Sweden, from 1 January 2013 to 31 December 2016. The ACS delivery intervals were compared between groups of women with various clinical scenarios and related to neonatal outcomes. RESULTS: The study included 498 preterm neonates from 431 women. One to seven days before delivery, 41% of the women received ACS. Women with preterm prelabor rupture of membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight days, respectively, compared with women with maternal/fetal indications or preterm labor (three and two days, respectively) (p < 0.001). Neonates with an ACS delivery interval of more than seven days were at a higher risk of respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI) 1.05-3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI 1.45-5.33) than were neonates with an ACS delivery interval of one to seven days. CONCLUSION: Optimal timing of ACS treatment varied significantly based on the clinical indication. Women with preterm prelabor rupture of membranes or vaginal bleeding were more likely to have an ACS delivery interval of more than seven days. A prolonged ACS delivery interval was associated with an increased risk of neonatal respiratory morbidity and a prolonged stay in the neonatal care unit, but not with neonatal mortality.

Cerebral Palsy in Extremely Preterm Infants.

BACKGROUND AND OBJECTIVES: The risk of cerebral palsy (CP) is high in preterm infants and is often accompanied by additional neurodevelopmental comorbidities. The present study describes lifetime prevalence of CP in a population-based prospective cohort of children born extremely preterm, including the type and severity of CP and other comorbidities (ie, developmental delay and/or cognitive impairment, neurobehavioral morbidity, epilepsy, vision and hearing impairments), and overall severity of disability. In this study, we also evaluate whether age at assessment, overall severity of disability, and available sources of information influence outcome results. METHODS: All Swedish children born before 27 weeks' gestation from 2004 to 2007 were included (the Extremely Preterm Infants in Sweden Study). The combination of neonatal information, information from clinical examinations and neuropsychological assessments at 2.5 and 6.5 years of age, original medical chart reviews, and extended chart reviews was used. RESULTS: The outcome was identified in 467 (94.5%) of eligible children alive at 1 year of age. Forty-nine (10.5%) children had a lifetime diagnosis of CP, and 37 (76%) were ambulatory. Fourteen (29%) had CP diagnosed after 2.5 years of age, 37 (76%) had at least 1 additional comorbidity, and 27 (55%) had severe disability. The probability for an incomplete evaluation was higher in children with CP compared with children without CP. CONCLUSIONS: Children born extremely preterm with CP have various comorbidities and often overall severe disability. The importance of long-term follow-up and of obtaining comprehensive outcome information from several sources in children with disabilities is shown.

Guidelines for Cleaning Transvaginal Ultrasound Transducers Between Patients.

The purpose of this article is to provide guidance regarding the cleaning and disinfection of transvaginal ultrasound probes. These recommendations are also applicable to transrectal probes.