Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review.

OBJECTIVES: To conduct a systematic literature review to evaluate the global incidence of intraventricular hemorrhage grade 2-4 among extremely preterm infants. METHODS: We performed searches in MEDLINE and Embase for intraventricular hemorrhage and prematurity cited in English language observational studies published from May 2006 to October 2017. Included studies analyzed data from infants born at ≤28 weeks' gestational age and reported on intraventricular hemorrhage epidemiology. RESULTS: Ninety-eight eligible studies encompassed 39 articles from Europe, 31 from North America, 25 from Asia, five from Oceania, and none from Africa or South America; both Europe and North America were included in two publications. The reported global incidence range of intraventricular hemorrhage grade 3-4 was 5-52% (Europe: 5-52%; North America: 8-22%; Asia: 5-36%; Oceania: 8-13%). When only population-based studies were included, the incidence range of intraventricular hemorrhage grade 3-4 was 6-22%. The incidence range of intraventricular hemorrhage grade 2 was infrequently documented and ranged from 5-19% (including population-based studies). The incidence of intraventricular hemorrhage was generally inversely related to gestational age. CONCLUSIONS: Intraventricular hemorrhage is a frequent complication of extremely preterm birth. Intraventricular hemorrhage incidence range varies by region, and the global incidence of intraventricular hemorrhage grade 2 is not well documented.

Burden of Infection in Patients With and Without Secondary Immunodeficiency Disease Following Diagnosis of a Mature B Cell Malignancy.

BACKGROUND: This retrospective cohort study compared patient characteristics and burden of infection in patients with mature B cell malignancies with and without secondary immunodeficiency disease (SID). PATIENTS AND METHODS: Data were extracted from the Humedica database (H-DB) and Guardian Research Network (GRN) database from October 1, 2015 to March 10, 2020, including a 6-month pre-index period (PIP) and 12-month follow-up. Patients aged ≥18 years diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma, or non-Hodgkin's lymphoma in the PIP were stratified into 2 cohorts: SID (hypogammaglobulinemia [using ICD-10-CM codes] or serum IgG levels <5.0 g/L, both with signs and symptoms of SID or at least 1 infection) and no-SID. Patients with SID or primary immunodeficiency diseases in the PIP were excluded. RESULTS: Overall, 2221 patients with SID (H-DB/GRN: n = 1959/262), and 19,141 patients without SID (n = 17,598/1543) were included. Baseline characteristics were similar across cohorts. At 12-month follow-up, significantly more patients with SID had experienced ≥1 infection and ≥1 severe bacterial infection than those without SID (both P < .001). H-DB/GRN mean (standard deviation) number of severe bacterial infections was 7.6 (9.9)/2.9 (2.7) for the SID cohort versus 5.2 (6.8)/2.4 (2.2) for the no-SID cohort. CONCLUSION: This study confirms that patients with mature B cell malignancies and SID face a significantly higher burden of infections than those without SID.

Modeling travel impedance to medical care for children with birth defects using Geographic Information Systems.

BACKGROUND: Children with birth defects may face significant geographic barriers accessing medical care and specialized services. Using a Geographic Information Systems-based approach, one-way travel time and distance to access medical care for children born with spina bifida was estimated. METHODS: Using 2007 road information from the Florida Department of Transportation, we built a topological network of Florida roads. Live-born Florida infants with spina bifida during 1998 to 2007 were identified by the Florida Birth Defects Registry and linked to hospital discharge records. Maternal residence at delivery and hospitalization locations were identified during the first year of life. RESULTS: Of 668 infants with spina bifida, 8.1% (n = 54) could not be linked to inpatient data, resulting in 614 infants. Of those 614 infants, 99.7% (n = 612) of the maternal residential addresses at delivery were successfully geocoded. Infants with spina bifida living in rural areas in Florida experienced travel times almost twice as high compared with those living in urban areas. When aggregated at county levels, one-way network travel times exhibited statistically significant spatial autocorrelation, indicating that families living in some clusters of counties experienced substantially greater travel times compared with families living in other areas of Florida. CONCLUSION: This analysis demonstrates the usefulness of linking birth defects registry and hospital discharge data to examine geographic differences in access to medical care. Geographic Information Systems methods are important in evaluating accessibility and geographic barriers to care and could be used among children with special health care needs, including children with birth defects.

Assessing the potential of polygenic scores to strengthen medical risk prediction models of COVID-19.

As findings on the epidemiological and genetic risk factors for coronavirus disease-19 (COVID-19) continue to accrue, their joint power and significance for prospective clinical applications remains virtually unexplored. Severity of symptoms in individuals affected by COVID-19 spans a broad spectrum, reflective of heterogeneous host susceptibilities across the population. Here, we assessed the utility of epidemiological risk factors to predict disease severity prospectively, and interrogated genetic information (polygenic scores) to evaluate whether they can provide further insights into symptom heterogeneity. A standard model was trained to predict severe COVID-19 based on principal component analysis and logistic regression based on information from eight known medical risk factors for COVID-19 measured before 2018. In UK Biobank participants of European ancestry, the model achieved a relatively high performance (area under the receiver operating characteristic curve ~90%). Polygenic scores for COVID-19 computed from summary statistics of the Covid19 Host Genetics Initiative displayed significant associations with COVID-19 in the UK Biobank (p-values as low as 3.96e-9, all with R2 under 1%), but were unable to robustly improve predictive performance of the non-genetic factors. However, error analysis of the non-genetic models suggested that affected individuals misclassified by the medical risk factors (predicted low risk but actual high risk) display a small but consistent increase in polygenic scores. Overall, the results indicate that simple models based on health-related epidemiological factors measured years before COVID-19 onset can achieve high predictive power. Associations between COVID-19 and genetic factors were statistically robust, but currently they have limited predictive power for translational settings. Despite that, the outcomes also suggest that severely affected cases with a medical history profile of low risk might be partly explained by polygenic factors, prompting development of boosted COVID-19 polygenic models based on new data and tools to aid risk-prediction.

Improved survival among children with spina bifida in the United States.

OBJECTIVE: To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. STUDY DESIGN: A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. RESULTS: During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. CONCLUSIONS: The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival.

Prevalence of esophageal atresia among 18 international birth defects surveillance programs.

BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35-2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954-4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012.

The clinical burden of extremely preterm birth in a large medical records database in the United States: Mortality and survival associated with selected complications.

BACKGROUND: Preterm birth is a leading cause of infant mortality, particularly for those born extremely prematurely (EP; <28 weeks' gestational age [GA]). Survivors are predisposed to complications such as bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). AIMS: To examine the epidemiology, complications, and mortality/survival among EP infants. STUDY DESIGN: Retrospective analysis of electronic medical records from the Kaiser Permanente Northern California database. SUBJECTS: EP infants live-born between 22 and <28 weeks' GA from 1997 to 2016. OUTCOME MEASURES: Cumulative all-cause mortality/survival were analyzed and stratified by GA (22 to <24, 24 to <26, 26 to <28 weeks), complications (BPD/CLD, IVH, ROP), and birth period (1997 to 2003, 2004 to 2009, 2010 to 2016). Cox proportional hazard models were constructed to assess the mortality risk associated with BPD/CLD or IVH. RESULTS: 2154 EP infants were identified; of these, 916 deaths were recorded. Mortality was highest during the first 3 months (41.7 % cumulative mortality), and few were reported after 2 years (42.5 % cumulative mortality). Mortality decreased with higher GA and over more recent birth periods. BPD/CLD and IVH grade 3/4 were associated with increased mortality risk versus no complications (adjusted hazard ratios 1.41 and 1.78, respectively). CONCLUSIONS: The risk of mortality is high during the first few months of life for EP infants, and is even higher for those with BPD and IVH. Despite an overall trend toward increased survival for EP infants, strategies targeting survival of EP infants with these complications are needed.

Long-term burden of respiratory complications associated with extreme prematurity: An analysis of US Medicaid claims.

BACKGROUND: Infants born extremely premature (EP) (<28 weeks gestational age) are at high risk of complications, particularly bronchopulmonary dysplasia (BPD), which can develop into chronic lung disease (CLD). METHODS: The burden of respiratory complications in EP infants up to 2 years corrected age (CA) was evaluated using real-world data from the US Medicaid program. Data recorded between 1997 and 2018 on EP infants without major congenital malformations were collected from Medicaid records of six states. EP infants were divided into three cohorts: BPD, CLD, and without BPD or CLD. The incidence of respiratory conditions, respiratory medication use, and healthcare resource utilization were compared between the BPD cohort and CLD cohort versus the cohort without BPD or CLD, using unadjusted and adjusted generalized linear models. RESULTS: A total of 4462 EP infants were identified (17.4% of all premature infants in the database). Of these, BPD and CLD were diagnosed in 61.9% and 72.1%, respectively, and 14.5% were diagnosed with neither BPD nor CLD. Compared with infants without BPD or CLD, infants with BPD or CLD had more complications and a longer length of birth hospitalization stay. Respiratory distress syndrome was the most frequently reported complication (94.6%, 92.5%, and 82.3% of EP infants in the BPD, CLD, and without BPD or CLD cohorts, respectively). After the birth hospitalization, respiratory conditions, respiratory medication use, and incidence rates of rehospitalizations, emergency room visits, and outpatient visits were higher for infants with BPD or CLD. Rehospitalization occurred in 50.5%, 51.6%, and 27.3% of EP infants with BPD, CLD, or without BPD or CLD, respectively; most hospitalizations occurred for respiratory-related reasons. CONCLUSION: In this analysis of a large population of EP infants up to 2 years CA, respiratory conditions were prevalent after the birth hospitalization and were associated with high rates of medication and healthcare resource utilization.

The clinical burden of extremely preterm birth in a large medical records database in the United States: complications, medication use, and healthcare resource utilization.

INTRODUCTION: Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28 weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system. METHODS: The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3 years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22 weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (≤1 year, >1 year and ≤2 years, and >2 years and ≤3 years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits. RESULTS: A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3 years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3 years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition. CONCLUSIONS: The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3 years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term.

Phocomelia: a worldwide descriptive epidemiologic study in a large series of cases from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature.

Epidemiologic data on phocomelia are scarce. This study presents an epidemiologic analysis of the largest series of phocomelia cases known to date. Data were provided by 19 birth defect surveillance programs, all members of the International Clearinghouse for Birth Defects Surveillance and Research. Depending on the program, data corresponded to a period from 1968 through 2006. A total of 22,740,933 live births, stillbirths and, for some programs, elective terminations of pregnancy for fetal anomaly (ETOPFA) were monitored. After a detailed review of clinical data, only true phocomelia cases were included. Descriptive data are presented and additional analyses compared isolated cases with those with multiple congenital anomalies (MCA), excluding syndromes. We also briefly compared congenital anomalies associated with nonsyndromic phocomelia with those presented with amelia, another rare severe congenital limb defect. A total of 141 phocomelia cases registered gave an overall total prevalence of 0.62 per 100,000 births (95% confidence interval: 0.52-0.73). Three programs (Australia Victoria, South America ECLAMC, Italy North East) had significantly different prevalence estimates. Most cases (53.2%) had isolated phocomelia, while 9.9% had syndromes. Most nonsyndromic cases were monomelic (55.9%), with an excess of left (64.9%) and upper limb (64.9%) involvement. Most nonsyndromic cases (66.9%) were live births; most isolated cases (57.9%) weighed more than 2,499 g; most MCA (60.7%) weighed less than 2,500 g, and were more likely stillbirths (30.8%) or ETOPFA (15.4%) than isolated cases. The most common associated defects were musculoskeletal, cardiac, and intestinal. Epidemiological differences between phocomelia and amelia highlighted possible differences in their causes.

Conjoined twins: a worldwide collaborative epidemiological study of the International Clearinghouse for Birth Defects Surveillance and Research.

Conjoined twins (CT) are a very rare developmental accident of uncertain etiology. Prevalence has been previously estimated to be 1 in 50,000 to 1 in 100,000 births. The process by which monozygotic twins do not fully separate but form CT is not well understood. The purpose of the present study was to analyze diverse epidemiological aspects of CT, including the different variables listed in the Introduction Section of this issue of the Journal. The study was made possible using the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) structure. This multicenter worldwide research includes the largest sample of CT ever studied. A total of 383 carefully reviewed sets of CT obtained from 26,138,837 births reported by 21 Clearinghouse Surveillance Programs (SP) were included in the analysis. Total prevalence was 1.47 per 100,000 births (95% CI: 1.32-1.62). Salient findings including an evident variation in prevalence among SPs: a marked variation in the type of pregnancy outcome, a similarity in the proportion of CT types among programs: a significant female predominance in CT: particularly of the thoracopagus type and a significant male predominance in parapagus and parasitic types: significant differences in prevalence by ethnicity and an apparent increasing prevalence trend in South American countries. No genetic, environmental or demographic significant associated factors were identified. Further work in epidemiology and molecular research is necessary to understand the etiology and pathogenesis involved in the development of this fascinating phenomenon of nature.

Bladder exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research, and an overview of the literature.

Bladder exstrophy (BE) is a complex congenital anomaly characterized by a defect in the closure of the lower abdominal wall and bladder. We aimed to provide an overview of the literature and conduct an epidemiologic study to describe the prevalence, and maternal and case characteristics of BE. We used data from 22 participating member programs of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). All cases were reviewed and classified as isolated, syndrome, and multiple congenital anomalies. We estimated the total prevalence of BE and calculated the frequency and odds ratios for various maternal and case characteristics. A total of 546 cases with BE were identified among 26,355,094 births. The total prevalence of BE was 2.07 per 100,000 births (95% CI: 1.90-2.25) and varied between 0.52 and 4.63 among surveillance programs participating in the study. BE was nearly twice as common among male as among female cases. The proportion of isolated cases was 71%. Prevalence appeared to increase with increasing categories of maternal age, particularly among isolated cases. The total prevalence of BE showed some variations by geographical region, which is most likely attributable to differences in registration of cases. The higher total prevalence among male cases and older mothers, especially among isolated cases, warrants further attention.

Cloacal exstrophy: an epidemiologic study from the International Clearinghouse for Birth Defects Surveillance and Research.

Cloacal exstrophy presents as a complex abdominal wall defect thought to result from a mesodermal abnormality. Anatomically, its main components are Omphalocele, bladder Exstrophy and Imperforate anus. Other associated malformations include renal malformations and Spine defects (OEIS complex). Historically, the prevalence ranges from 1 in 200,000 to 400,000 births, with higher rates in females. Cloacal exstrophy is likely etiologically heterogeneous as suggested by its recurrence in families and occurrence in monozygotic twins. The defect has been described in infants with limb-body wall, with trisomy 18, and in one pregnancy exposed to Dilantin and diazepam. Due to its rarity, the use of a nonspecific diagnostic code for case identification, and lack of validation of the clinical findings, cloacal exstrophy remains an epidemiologic challenge. The purpose of this study was to describe the prevalence, associated anomalies and maternal characteristics among infants born with cloacal exstrophy. We used data from the International Clearinghouse for Birth Defects Surveillance and Research submitted from 18 birth defect surveillance programs representing 24 countries. Cases were clinically evaluated locally and reviewed centrally by two authors. Cases of persistent cloaca were excluded. A total of 186 cases of cloacal exstrophy were identified. Overall prevalence was 1 in 131,579 births: ranging from 1 in 44,444 births in Wales to 1 in 269,464 births in South America. Live birth prevalence was 1 in 184,195 births. Prevalence ratios did not vary by maternal age. Forty-two (22.6%) cases met the criteria for the OEIS complex, whereas 60 (32.3%) were classified as OEI and 18 (9.7%) as EIS (one with suspected VATER (0.5%)). Other findings included two cases with trisomy 13 (one without a karyotype confirmation), one with mosaic trisomy 12 (0.5%), one with mosaic 45,X (0.5%) and one classified as having amnion band sequence (0.5%). Twenty-seven (14.5%) infants had other anomalies unrelated to cloacal exstrophy. Cloacal exstrophy is a rare anomaly with variability in prevalence by geographic location. The proportion of cases classified as OEIS complex was lower in this study than previously reported. Among all cases, 54.8% were reported to have an omphalocele.

Amelia: a multi-center descriptive epidemiologic study in a large dataset from the International Clearinghouse for Birth Defects Surveillance and Research, and overview of the literature.

This study describes the epidemiology of congenital amelia (absence of limb/s), using the largest series of cases known to date. Data were gathered by 20 surveillance programs on congenital anomalies, all International Clearinghouse for Birth Defects Surveillance and Research members, from all continents but Africa, from 1968 to 2006, depending on the program. Reported clinical information on cases was thoroughly reviewed to identify those strictly meeting the definition of amelia. Those with amniotic bands or limb-body wall complex were excluded. The primary epidemiological analyses focused on isolated cases and those with multiple congenital anomalies (MCA). A total of 326 amelia cases were ascertained among 23,110,591 live births, stillbirths and (for some programs) elective terminations of pregnancy for fetal anomalies. The overall total prevalence was 1.41 per 100,000 (95% confidence interval: 1.26-1.57). Only China Beijing and Mexico RYVEMCE had total prevalences, which were significantly higher than this overall total prevalence. Some under-registration could influence the total prevalence in some programs. Liveborn cases represented 54.6% of total. Among monomelic cases (representing 65.2% of nonsyndromic amelia cases), both sides were equally involved, and the upper limbs (53.9%) were slightly more frequently affected. One of the most interesting findings was a higher prevalence of amelia among offspring of mothers younger than 20 years. Sixty-nine percent of the cases had MCA or syndromes. The most frequent defects associated with amelia were other types of musculoskeletal defects, intestinal, some renal and genital defects, oral clefts, defects of cardiac septa, and anencephaly.

Maternal age and prevalence of isolated congenital heart defects in an urban area of the United States.

Although maternal age has been associated with a number of birth defects in several reports, the literature on the association of maternal age with isolated congenital heart defect (CHD) phenotypes has been limited. We evaluated CHD prevalence based on a cohort of 5,289 infants and fetuses with isolated CHDs born during the period 1968-2005 and ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP) among residents of five central counties in Atlanta. For our denominator, we obtained information on births to residents of the same counties from vital records (n = 1,301,143). We calculated prevalence ratios for 23 CHD phenotypes by several maternal age categories, using the group 25-29 years of age as a reference group. We used Poisson regression models to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for maternal race, infant sex, and birth cohort. A maternal age of 35 years or older was associated with an increased prevalence for several CHD phenotypes: laterality defects (aPR = 2.06; CI 1.22-3.48), all conotruncal defects (aPR = 1.30; CI 1.03-1.65), and specifically for dextro-transposition of the great arteries (aPR = 1.65; CI 1.10-2.48), coarctation of the aorta (aPR = 1.54; CI 1.10-2.16), ventricular septal defects (aPR = 1.20; CI 1.06-1.36), and atrial septal defects (aPR = 1.36; CI 1.05-1.77). Our findings suggest that the birth prevalence of specific isolated CHDs varies with maternal age. Further studies are warranted to corroborate these observations, taking into account potential confounding by known modifiable risk factors.

Global prevalence of long-term neurodevelopmental impairment following extremely preterm birth: a systematic literature review.

OBJECTIVE: Neurodevelopmental impairment (NDI) is a major complication of extreme prematurity. This systematic review was conducted to summarize the worldwide long-term prevalence of NDI associated with extreme prematurity. METHODS: Embase and MEDLINE databases were searched for epidemiologic and observational/real-world studies, published in English between 2011 and 2016, reporting long-term prevalence of NDI (occurring from 1 year) among extremely preterm infants born at gestational age (GA) ≤28 weeks. RESULTS: Of 2406 articles identified through searches, 69 met the protocol NDI definition (24 North America, 25 Europe, 20 Rest of World). Prevalence of any severity NDI in North America was 8%-59% at 18 months to 2 years, and 11%-37% at 2-5 years; prevalence of moderate NDI in Europe was 10%-13% at 18 months to 2 years, 3% at 2-5 years, and 9%-19% at ≥5 years; prevalence of any NDI in Rest of World was 15%-61% at 18 months to 2 years, and 42% at 2-5 years (no North America/Rest of World studies reported any NDI at ≥5 years). A trend toward higher prevalence of NDI with lower GA at birth was observed. CONCLUSIONS: Extreme prematurity has a significant long-term worldwide impact on neurodevelopmental outcomes.

Global incidence of bronchopulmonary dysplasia among extremely preterm infants: a systematic literature review.

BACKGROUND: Infants born extremely preterm (<28 weeks gestational age (GA)) face a high risk of neonatal mortality. Bronchopulmonary dysplasia (BPD) is the most common morbidity of prematurity. OBJECTIVE: To evaluate the global incidence of BPD among infants born extremely preterm. DESIGN: A systematic review of the literature was conducted in Embase and MEDLINE (via PubMed) using a prespecified search strategy for BPD and prematurity. Observational studies published in English between 16 May 2006 and 16 October 2017 reporting on the occurrence of BPD in infants born <28 weeks GA were included. RESULTS: Literature searches yielded 103 eligible studies encompassing 37 publications from Europe, 38 publications from North America, two publications from Europe and North America, 19 publications from Asia, one publication from Asia and North America, six publications from Oceania, and zero publications from Africa or South America. The reported global incidence range of BPD was 10-89% (10-73% in Europe, 18-89% in North America, 18-82% in Asia, and 30-62% in Oceania). When only population-based observational studies that defined BPD as requiring supplemental oxygen at 36 weeks postmenstrual age were included, the global incidence range of BPD was 17-75%. The wide range of incidences reflected interstudy differences in GA (which was inversely related to BPD incidence), birthweight, and survival rates across populations and institutions. CONCLUSIONS: BPD is a common health morbidity occurring with extremely preterm birth. Further study of factors that impact incidence, aside from low GA, may help to elucidate modifiable risks.

Respiratory morbidity, healthcare resource use, and cost burden associated with extremely preterm birth in The Netherlands.

BACKGROUND: Extremely preterm (EP) infants have high rates of respiratory morbidity and correspondingly high healthcare resource utilization. OBJECTIVES: Data from the PHARMO Perinatal Research Network were analyzed to quantify the burden of EP birth in the Netherlands. METHODS: A retrospective analysis included infants <28 weeks gestational age with a birth record in the Perinatal Registry (1999-2015) and data in the PHARMO Database Network. Outcomes of interest included select comorbidities, hospital readmissions, and costs of hospitalization and medication up to 1- and 2-years corrected age. Outcomes were stratified by birth period (1999-2005, 2000-2009, 2010-2015) and by diagnosis of bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD). RESULTS: The cohort included 168 EP infants (37 born 1999-2005, 51 born 2006-2009, 80 born 2010-2015). Median (Q1-Q3) birth weights decreased by birth period from 970 (840-1,035) g in 1999-2005 to 853 (695-983) g in 2010-2015. Overall, BPD and CLD were reported during the birth hospitalization in 40% and 29% of infants, respectively; rates of BPD increased and rates of CLD decreased by birth period. Eighty-four percent of EP infants had an additional comorbidity. Mean (standard deviation) costs of birth hospitalization were €110,600 (€73,000) for 1999-2005, €119,350 (€60,650) for 2006-2009, and €138,800 (€130,100) for 2010-2015. Birth hospitalization and total costs for up to 1- and 2-years corrected age were higher for infants with BPD and/or CLD than for those without either complication. CONCLUSION: Healthcare resource utilization and costs for EP infants, especially for those with respiratory morbidities, increased between 1999 and 2015. Future cost-effectiveness analyses are essential to determine the economic impact of this change and underscore the need for new therapeutic interventions to decrease clinical sequelae in this vulnerable population.

Patient-reported burden of dry eye disease in the UK: a cross-sectional web-based survey.

OBJECTIVES: To compare sociodemographics and vision-related quality of life (QoL) of individuals with or without dry eye disease (DED); and to explore the impact of DED symptom severity on visual function, activity limitations and work productivity. DESIGN: Cross-sectional web-based survey. SETTING: General UK population. PARTICIPANTS: Adults ≥18 years with (N=1002) or without (N=1003) self-reported DED recruited through email and screened. MAIN OUTCOME MEASURES: All participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25), with six additional questions (items A3-A8), and the EuroQol 5 dimensions 5 levels. DED participants also completed Impact of Dry Eye on Everyday Life questionnaire, 5-item Dry Eye Questionnaire and the Standardised Patient Evaluation of Eye Dryness questionnaire along with the Ocular Comfort Index, Work Productivity and Activity Impairment and the Eye Dryness Score (EDS), a Visual Analogue Scale. RESULTS: Baseline demographic and clinical characteristics were similar in participants with versus without DED (mean age, 55.2 vs 55.0 years; 61.8% vs 61.0% women, respectively) based on recruitment targets. Scores were derived from NEI VFQ-25 using the new 28-item revised VFQ (VFQ-28R) scoring. Mean (SD) VFQ-28R scores were lower in participants with versus without DED, indicating worse functioning (activity limitations, 73.3 (12.3) vs 84.4 (12.3); socioemotional functioning, 75.3 (21.5) vs 90.3 (16.2); total score, 71.6 (12.8) vs 83.6 (12.6)). Higher percentages of problems/inability to do activities were observed among those with versus without DED. The impact of DED on visual function was worse for participants with more severe DED symptoms, as assessed by EDS. In addition, a higher EDS was associated with worse symptoms on common DED scales and a worse impact on work productivity. CONCLUSIONS: DED symptoms were associated with negative effects on visual function, activities and work productivity, whereas worse DED symptoms had a greater impact on vision-related QoL and work productivity.

Long-term survival of infants with atrioventricular septal defects.

OBJECTIVE: To examine the variation in survival in infants with atrioventricular septal defects (AVSD) with demographic factors and clinical characteristics, including the presence of Down syndrome. STUDY DESIGN: We selected infants with all types of AVSD with Down syndrome (n = 177) and without Down syndrome (n = 161), born between Jan 1, 1979, and Dec 31, 2003 and identified through the Metropolitan Atlanta Congenital Defects Program (MACDP). Infants were classified by the complexity of their cardiac defects and presence of major non-cardiac malformations. Deaths (n = 111) were identified through 2004 with linkage with state vital records and the National Death Index. Kaplan-Meier survival probabilities and adjusted hazard ratios (HRs) were calculated in relation to demographic and clinical characteristics. RESULTS: Children with AVSD and Down syndrome had a similar overall survival probability (70%) as those without Down syndrome (69%). Mortality was higher in children with a complex AVSD (adjusted HR = 7.0; 95% CI, 3.1-15.5) and in children with > or =2 major non-cardiac malformations (adjusted HR = 3.4; 95% CI, 1.8-6.5) and was lower in children in the 1992 to 2003 birth cohort (adjusted HR = 0.6; 95% CI, 0.4-0.998). CONCLUSIONS: Down syndrome was not a prognostic factor. Our findings might be helpful in assessing the long-term prognosis of infants with AVSD.