Surveillance of ventricular septal defects in Delaware.

BACKGROUND: The prevalence of ventricular septal defects (VSDs), a birth defect in which there is an opening in the wall that separates the left and right ventricles of the heart, seemed to be substantially higher in Delaware compared with the National Birth Defects Prevention Network (NBDPN). The Delaware Birth Defects Registry (BDR) noted their high prevalence of VSDs in comparison with other states. METHODS: A subset of children with a VSD born in 2007 through 2010 was identified from the complete reportable statewide defect list that the BDR creates each year. VSDs were categorized by type of VSD (muscular, perimembranous, conotruncal, or atrioventricular septal defect), by either isolated or complex, and then by spontaneously closed, surgically closed, open but clinically insignificant, lost to follow-up, fetal or neonatal death. RESULTS: The BDR team found a prevalence of VSD of 83.4 per 10,000 including fetal/neonatal deaths. Excluding fetal and neonatal deaths the prevalence was 78.7 per 10,000 live births. Excluding small muscular VSDs, the prevalence in Delaware falls to 25.7 per 10,000. CONCLUSION: The BDR team chose to include all babies with all types of VSDs. Using these criteria Delaware's prevalence of 78.7 was higher than that reported by other states (whose prevalence ranges from 1.6 to 70.0 per 10,000 live births) (National Birth Defects Prevention Network, ). Delaware's prevalence is similar to other states when small muscular VSDs are excluded. Birth Defects Research (Part A) 106:888-893, 2016. © 2016 Wiley Periodicals, Inc.

Restrictive Dermopathy: A Rare Disease with Unusual Radiographic Findings.

The patient is a unique case presenting with presumed Restrictive Dermopathy (RD) and intracranial and adrenal calcifications, an association not previously described in the literature. This case postulates the possibility of additional radiographic features that can be included in the spectrum of RD or as secondary events from the underlying pathophysiology of RD.

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.

IMPORTANCE: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES: To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN: Epidemiological and retrospective observational study. SETTING: Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES: Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE: Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

Assessing the relationship between neonatal abstinence syndrome and birth defects in Delaware.

BACKGROUND: Neonatal abstinence syndrome (NAS) is a withdrawal syndrome in newborns and is frequently caused by maternal opioid use during pregnancy. Our study examines whether NAS is associated with birth defects in Delaware. METHODS: We conducted a retrospective analysis of linked Delaware birth certificate data (BCD), hospital discharge data (HDD), and birth defects registry (BDR) data to examine the association between NAS and birth defects for all hospital births to Delaware residents from 2010 to 2017. Birth defects data were abstracted from medical records from Delaware's BDR. We used International Classification of Diseases Ninth and Tenth Revision Clinical Modification (ICD-9-CM/ICD-10-CM) 779.5 and P96.1 codes to determine NAS using HDD and excluded iatrogenic cases of NAS. We estimated crude and adjusted odds ratio with 95% confidence intervals (CIs). RESULTS: During 2010-2017, there were 2,784 cases of birth defects and 1,651 cases of NAS in Delaware. Among infants with a diagnosis of NAS, 56 also had a birth defect (3.4%), similar to 2,728 birth defects among 79,636 infants without a diagnosis of NAS (3.4%). We found no statistically significant association between an NAS diagnosis and birth defects (adjusted odds ratios = 1.0; 95% CI: 0.8-1.3). CONCLUSIONS: Our multiyear state-wide study using linked BCD, HDD, and BDR data for Delaware did not show a statistically significant association between infants diagnosed with NAS and birth defects, overall.

Increasing illness severity in very low birth weight infants over a 9-year period.

BACKGROUND: Recent reports have documented a leveling-off of survival rates in preterm infants through the 1990's. The objective of this study was to determine temporal changes in illness severity in very low birth weight (VLBW) infants in relationship to the outcomes of death and/or severe IVH. METHODS: Cohort study of 1414 VLBW infants cared for in a single level III neonatal intensive care unit in Delaware from 1993-2002. Infants were divided into consecutive 3-year cohorts. Illness severity was measured by two objective methods: the Score for Neonatal Acute Physiology (SNAP), based on data from the 1st day of life, and total thyroxine (T4), measured on the 5th day of life. Death before hospital discharge and severe intraventricular hemorrhage (IVH) were investigated in the study sample in relation to illness severity. The fetal death rate was also investigated. Statistical analyses included both univariate and multivariate analysis. RESULTS: Illness severity, as measured by SNAP and T4, increased steadily over the 9-year study period with an associated increase in severe IVH and the combined outcome of death and/or severe IVH. During the final 3 years of the study, the observed increase in illness severity accounted for 86% (95% CI 57-116%) of the variability in the increase in death and/or severe IVH. The fetal death rate dropped from 7.8/1000 (1993-1996) to 5.3/1000 (1999-2002, p = .01) over the course of the study. CONCLUSION: These data demonstrate a progressive increase in illness in VLBW infants over time, associated with an increase in death and/or severe IVH. We speculate that the observed decrease in fetal death, and the increase in neonatal illness, mortality and/or severe IVH over time represent a shift of severely compromised patients that now survive the fetal time period and are presented for care in the neonatal unit.

Newborn screening levels of 17-hydroxyprogesterone in very low birth weight infants and the relationship to chronic lung disease.

OBJECTIVES: 17-Hydroxyprogesterone (17-OHP), an intermediary hormone in cortisol synthesis, has been shown to be elevated in premature infants. However, the relationship between levels of 17-OHP with chronic lung disease (CLD) have not been extensively explored. The objective of this study was to determine whether there is an association between CLD and levels of 17-OHP in a population of very low birth weight infants. STUDY DESIGN: Cohort study of very low birth weight infants cared for at a single level 3 NICU during a 3-year period from July 2001-July 2004, n=435. Infants had a minimum of one screen for 17-OHP. 17-OHP was measured on the 5th day of life and at 2-4 weeks of life as part of the State of Delaware Newborn Screening Program. Statistical analysis included chi-squared, Pearson correlation, and logistic regression. RESULTS: Levels of 17-OHP were higher at the time of the 1st screen compared to the 2nd screen (42.2 +/- 36.7 vs 23.5 +/- 32.3 ng/ml, respectively, p = 0.01). After controlling for potential confounding variables, gestational age and prenatal steroids were independently associated with 17-OHP. However, logistic regression analysis showed no association between a 1 log increase in levels of 17-OHP with the outcomes of CLD (odds ratio 1.7, 95% CI 0.7-3.8), or death and/or CLD (odds ratio 2.1, 95% CI 0.9-4.8). CONCLUSIONS: In our population of very low birth weight infants elevated levels of 17-OHP were not associated with the development of CLD.

Admission thyroid evaluation in very-low-birth-weight infants: association with death and severe intraventricular hemorrhage.

OBJECTIVES: To determine if thyroxine (T(4)) and thyrotropin (TSH) levels, measured at the time of admission to the neonatal intensive care unit, are associated with the outcomes of death and/or severe intraventricular hemorrhage (IVH). STUDY DESIGN: Blood for total T(4) and TSH was obtained upon admission to the neonatal intensive care unit in infants with birthweights less than 1500 g. Infants were followed until hospital discharge. Statistical analysis included one-way analysis of variance, Pearson correlation, and logistic regression. Data are expressed as mean +/- standard deviation (SD). RESULTS: One hundred twenty-two infants were enrolled. The mean gestational age of the study population was 27 +/- 2.8 weeks. Both T(4) (R = 0.25, p < 0.01) and TSH (R = 0.39, p < 0.01) at the time of admission correlated with gestational age. Infants who died and/or had severe IVH (n = 31) had lower T(4) (5.0 +/- 2.1 vs. 8.4 +/- 4.1 microg/dL, p < 0.01) and lower TSH (5.5 +/- 6.0 vs. 18.1 +/- 18.1 microIU/mL, p = 0.03) at the time of admission compared to infants who survived without severe IVH. After controlling for gestational age, low T(4) remained associated with an increased odds of death and/or severe IVH (odds ratio for every 1 microg/dL decrease in T(4): 1.4, 95% confidence interval 1.1-1.7). CONCLUSIONS: Our data show that both low total T(4) and TSH, measured at the time of nursery admission, are associated with death and severe intraventricular hemorrhage. Our data suggest that it may be feasible to design a study of early T(4) supplementation to determine potential benefit in infants with the lowest T(4) values rather than treating based on associated factors such as gestational age.

Factors influencing levels of 17-hydroxyprogesterone in very low birth weight infants and the relationship to death and IVH.

OBJECTIVES: 17-Hydroxyprogesterone, an intermediary hormone in cortisol synthesis, has been shown to be elevated in premature infants. However, the relationship between levels of 17-hydroxyprogesterone with death and intraventricular hemorrhage has not been extensively explored. The objective of this study was to determine the factors influencing 17-hydroxyprogesterone and determine if there is an association between intraventricular hemorrhage, mortality, and levels of 17-hydroxyprogesterone in a population of very low birth weight infants. STUDY DESIGN: Cohort study of very low birth weight infants cared for at a single level 3 NICU during a 1-year period from July 2001 to July 2002. Infants had a minimum of one screen for 17-hydroxyprogesterone and one cranial sonogram. 17-Hydroxyprogesterone was measured on the fifth day of life and at 2 to 4 weeks of life as part of the State of Delaware Newborn Screening Program. Statistical analysis included chi(2), Pearson correlation, multiple-linear regression, and logistic regression. RESULTS: Levels of 17-hydroxyprogesterone were higher at the time of the first screen compared to the second screen (28.3+/-25.6 vs 17.0+/-18.0 ng/ml, p=0.01), respectively. After controlling for potential confounding variables, gestational age, T(4), and prenatal steroids were all independently associated with 17-hydroxyprogesterone. However, logistic regression analysis showed no association between a 1 log increase in levels of 17-hydroxyprogesterone with the outcomes of death (odds ratio 1.8, 95% CI 0.6 to 5.6), severe IVH (0.7, 0.3 to 1.7), and death and/or severe intraventricular hemorrhage (0.9, 0.4 to 2.1). CONCLUSIONS: In our population of very low birth weight infants, low gestational age, low T(4), and prenatal steroids were all associated with an elevation in levels of 17-hydroxyprogesterone. High levels of 17-hydroxyprogesterone were not associated with death and/or severe IVH. Our data indicate that factors such as gestational age and antenatal steroids must be considered when interpreting 17-hydroxyprogesterone results from newborn screening.

Newborn screening in Delaware.

Newborn screening for metabolic, hematologic, and endocrinologic disorders is a well-established public health function. Recent technological advances have made screening possible for more disorders. For many of these disorders, there is evidence that screening is effective; however, some of these disorders are rare, and their response to therapy and their natural history are not completely understood. A number of states have instituted "expanded" newborn screening utilizing a combination of established and new technologies. Other states, including Delaware, have studied the experiences of the states doing expanded screening and have decided to proceed with expanded screening as well. Since early 2003, Delaware has been screening newborns for about 25 disorders, including amino acidopathies, organic acidurias, fatty acid oxidation disorders, hemoglobinopathies, and endocrinopathies.

As the child with chronic disease grows up: transitioning adolescents with special health care needs to adult-centered health care.

The purpose of this article is to inform readers of the Delaware Medical Journal about the concept of transitional care for adolescents and young adults with chronic health care needs. This is a topic that has recently received national attention and was the subject of a supplement to Pediatrics in December 2002. The concept of transitional care bears special importance in Delaware as every year hundreds of children with chronic disease turn 18 and leave their pediatric providers. It is uncertain that these children resume their care with an adult health care provider, and there is almost always some lag in time as patients attempt to find an adult provider who is knowledgeable about their condition and willing to assume them as a patient. An even greater uncertainty is whether or not adult providers are prepared to take care of this new generation of adults with cyanotic congenital heart disease, spina bifida, cerebral palsy, and other conditions. This article explores some of these ideas and discusses what is available in the transition literature and where to go from here.

Thyroid function in late preterm infants in relation to mode of delivery and respiratory support.

The relationship between thyroid function, mode of delivery, and illness in infants 34-36 weeks' gestation has not been well studied. We hypothesized that infants born by cesarean delivery and those with increased illness would have a reduction in thyroxine (T4) following birth. Total T4 and thyroid-stimulating hormone were obtained at birth (Time 1) and between days 2 and 5 (Time 2). The study sample included 129 infants 34-36 weeks' gestation. There were no differences in total T4 between infants born by cesarean or vaginal delivery (p=0.18), or between those requiring respiratory support compared to infants not requiring respiratory support (p=0.09). At Time 2, 93% of the study population had a total T4 below one standard error of the reference laboratory mean. In our study sample, despite many infants having a low total T4, there was no association between total T4 levels, respiratory support, or mode of delivery.

Independent relation of maternal prenatal factors to early childhood obesity in the offspring.

OBJECTIVE: To examine the independent contribution of risk factors developing during pregnancy to subsequent risk of obesity in young children. METHODS: We conducted a historical cohort study using data from electronic medical records of mothers and their 3,302 singleton offspring born between 2004 and 2007 at a community-based obstetric facility who attended a 4-year well visit at a pediatric practice network. The child's body mass index (BMI) z score at age 4 years was studied in relation to the mother's gestational weight gain, gestational diabetes mellitus, gestational hypertension or preeclampsia, and prenatal tobacco use. Institute of Medicine categories defined excess and inadequate gestational weight gain at term. Analysis of variance and multiple linear regression were used to test their independent relation to BMI. RESULTS: Mothers were white (39%), African American (46%), and of Hispanic ethnicity (11%); 46% were privately insured. The association of net gestational weight gain with the child's BMI z score was significant after adjustment for prepregnancy maternal factors (P<.001); gestational diabetes mellitus, gestational hypertension, and tobacco use were not significant in adjusted models. Children of mothers with excess gestational weight gain had a higher mean BMI z score (P<.001) but a significant association was observed only for inadequate gestational weight gain after adjusting for prepregnancy BMI and other covariates. Prepregnancy BMI (P<.001), Hispanic ethnicity (P<.001), and being married (P<.05) were independently associated with increasing BMI z score of the offspring. CONCLUSIONS: Preconception maternal factors had a greater influence on child obesity than prenatal factors. The gestational weight gain category was independently related to BMI z score of 4 year olds, but this association was significant only for mothers with inadequate gestational weight gain. LEVEL OF EVIDENCE: II.

Ophthalmologic disorders in children with syndromic and nonsyndromic hearing loss.

OBJECTIVE: To determine the rate of ophthalmologic anomalies among patients with syndromic and nonsyndromic, congenital sensorineural hearing loss (SNHL) to assess the need for comprehensive ophthalmologic evaluation in these children. DESIGN: Retrospective medical chart review of children with SNHL who underwent comprehensive evaluation by pediatric ophthalmologists and geneticists. SETTING: Tertiary care pediatric hospital. PATIENTS: Seventy-seven patients with SNHL. MAIN OUTCOME MEASURES: Degree of hearing loss (HL) and presence of ophthalmologic and genetic disorders. RESULTS: The overall rate of ophthalmologic disorders was 32% (25 of 77 patients). When children with multisystem genetic disorders known to be related to visual loss were excluded, the rate fell to 23% (12 of 53 vs 13 of 24; P = .006). There was no statistically significant difference in the degree of HL between patients with and without eye disorders (mean [SD], 46.5 [29.9] vs 49.1 [32.3] dB HL; P = .75). Patients with eye disorders were significantly more likely to have a multisystem genetic disorder (13 of 25 [52%] vs 11 of 52 [21%]; P = .006). No patients with ocular abnormalities had isolated otologic disorders, but 9 of 52 (17%) of those patients without ocular abnormalities did. CONCLUSIONS: Comprehensive ophthalmologic examination revealed a rate of ophthalmologic disorders in children with SNHL in the lower end of the previously reported rates of 31% to 61%. Children with nonsyndromic SNHL have an approximately 2- to 3-fold increase in ocular abnormalities compared with the general pediatric population. Ophthalmologic and genetic consultations are warranted in patients with congenital SNHL.

Hypothyroxinemia in mechanically ventilated term infants is associated with increased use of rescue therapies.

OBJECTIVE: Although common in preterm infants, transient hypothyroxinemia (TH) has not been investigated extensively in ill term infants. The objectives of this study were to investigate serum thyroxine (T4) and thyroid-stimulating hormone (TSH) in sick term infants and to determine whether there is any association between measures of thyroid function and short-term outcome in term infants who receive mechanical ventilation. METHODS: The investigation consisted of both a prospective observational study and a retrospective cohort study. In the prospective study, T4 and TSH were measured after birth in a group of sick term infants (n = 38) and compared with a group of well term infants (n = 18). Infants in the sick group received mechanical ventilation or continuous positive airway pressure and/or had neonatal seizures. Illness severity was quantified using the Score for Neonatal Acute Physiology. The retrospective cohort study included term infants who required mechanical ventilation and were born over a 5-year period (n = 347). Routine T4 screening was collected on the fifth day of life. TH was diagnosed in infants with a T4 <10%, with a TSH <25 microIU/mL. Clinical outcomes in infants with TH were compared with infants without TH. RESULTS: In the prospective study, infants in the sick group had lower T4 on the fifth day of life as compared with infants in the well group (11.7 +/- 4.9 vs 18.9 +/- 5.4 microg/dL), and 34% of infants in the sick group had a T4 <10th percentile compared with 6% of infants in the well group. T4 on day of life 5 was inversely correlated with Score for Neonatal Acute Physiology (R = -0.52). In the retrospective study, 21% of mechanically ventilated infants developed TH and were given statistically more inhaled nitric oxide, high-frequency ventilation, vasopressors, and pharmacologic paralysis when compared with infants without TH. Moreover, infants with TH were statistically more likely to die or require transfer to an extracorporeal membrane oxygenation center compared with infants without TH. CONCLUSION: Our data show that, similar to preterm infants, ill term infants develop TH. Term infants with TH required more intensive rescue interventions, including inhaled nitric oxide and transfer to an extracorporeal membrane oxygenation center. However, whether T4 levels are a marker or a mediator of clinical outcome remains to be determined.

Are perinatal risk factors helpful in predicting and optimizing treatment strategies for transient hypothyroxinemia in very-low-birth-weight infants?

Transient hypothyroxinemia is common in premature infants and has been associated with intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), poor neurodevelopmental outcomes, and mortality. Recent trials have failed to show that supplemental thyroid hormone improves overall neurodevelopmental outcome. The objective of this article is too determine perinatal risk factors for transient hypothyroxinemia (TH). We studied a cohort of infants born between July 1993 and July 2000 who were less than 1500 g and who received a newborn screening for thyroid function ( n = 932). Total serum thyroxine (T(4)) was collected routinely on the fifth day of life. T (4) was correlated with gestational age (R = 0.59, p < 0.01). After controlling for potential confounding variables, gestational age, dopamine, and mechanical ventilation were found to be independently associated with low T (4) (overall model: r(2) = 0.41, p < 0.01). Number needed to treat (NNT) analysis showed treating all infants less than 27 weeks would lead to treating 6.3 infants for every one with a subsequent T(4) < 5 microg/dL. By combining gestational age and need for dopamine support, NNT = 2.4 for every one infant with subsequent T(4) < 5 microg/dL. Low gestational age, mechanical ventilation, and need for dopamine were associated with low T(4) levels and may be helpful in optimizing treatment strategies for TH.