National rates of birth defects among hospitalized newborns

BACKGROUND: The Healthcare Cost and Utilization Project (HCUP) family of hospital discharge databases offer an unprecedented opportunity to generate national estimates of newborn infants with birth defects. This report estimates national hospital admissions for newborn infants diagnosed with birth defects computed from HCUP and compares them to pooled prevalence figures computed from state birth defect surveillance systems. METHODS: HCUP-derived rates of 36 birth defects from 1997 through 2001 were compared to rates derived from pooled data reported by 26 state-based surveillance systems stratified by inclusion of elective terminations in case definitions. Rate ratios (RRs) were calculated for each birth defect by dividing the rate derived from HCUP by the rate derived from the relevant surveillance systems. RESULTS: HCUP newborn hospitalization rates for birth defects closely approximate pooled birth defect rates for surveillance systems that do not include elective terminations. HCUP rates were not significantly different for 35 of 36 defects. Overall, 20 HCUP rates were within 10% of state rates, 11 more were within 20% of state rates, and only 1 differed by more than 50%. HCUP rates compared most closely to state rates for cardiovascular (VSD RR = 0.98, ASD = 0.96, pulmonary valve atresia and stenosis = 0.92), orofacial (cleft palate RR = 1.10, cleft lip = 1.06), and genitourinary defects (obstructive genitourinary RR = 1.01, bladder exstrophy = 0.97). HCUP rates compared less favorably to rates derived from surveillance systems that included elective terminations. CONCLUSIONS: HCUP data approximate state-based surveillance system data for defects that are easily recognized in the newborn period and infrequently a cause for elective termination. HCUP data can be used to examine the impact of public health efforts on the number of infants born with birth defects as well as the cost and consequences of variations in the hospital management of birth defects.     

Sensitivity, specificity, and positive predictive value of multiple malformations in isotretinoin embryopathy surveillance

Isotretinoin causes serious birth defects in about 25% of babies exposed in the first trimester of pregnancy. Despite warnings about the drug's teratogenicity, cases of isotretinoin embryopathy continue to occur; more than 80 such cases have been reported since 1982. The true magnitude of the problem is unknown, however, and case estimates range to more than 1,000. The need for isotretinoin embryopathy (IE) surveillance is therefore great. Sixty-one known cases were evaluated to determine the sensitivity (proportion of cases with a given defect pattern) of various defect combinations. Using data from the Metropolitan Atlanta Congenital Defects Program for the period before isotretinoin was available, we evaluated the specificity (proportion of malformed infants without exposure who do not have the pattern of defects) for the various defect combinations. Ear malformations (microtia, anotia, absence or stricture of auditory canal, missing pinnae) have an associated sensitivity of 70.5% and a specificity of 99.5%. Ear defects combined with central nervous system (CNS) defects (microcephalus, hydrocephalus, reduction deformities of the brain) and cardiovascular (CVS) defects (conotruncal defects, aortic arch abnormalities) have an associated sensitivity of 19.7% and a specificity of 100.0%. The case definition of ear defects combined with either CNS or CVS defects maximizes both specificity (99.9%) and sensitivity (45.9%). The investigators are now evaluating the feasibility of using this pattern of defects to monitor for IE within a national monitoring program.     

National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001

BACKGROUND: In the United States, birth defects affect approximately 3% of all births, are a leading cause of infant mortality, and contribute substantially to childhood morbidity. METHODS: Population-based data from the National Birth Defects Prevention Network were combined to estimate the prevalence of 21 selected defects for 1999-2001, stratified by surveillance system type. National prevalence was estimated for each defect by pooling data from 11 states with active case-finding, and adjusting for the racial/ethnic distribution of US live births. We also assessed racial/ethnic variation of the selected birth defects. RESULTS: National birth defect prevalence estimates ranged from 0.82 per 10,000 live births for truncus arteriosus to 13.65 per 10,000 live births for Down syndrome. Compared with infants of non-Hispanic (NH) white mothers, infants of NH black mothers had a significantly higher birth prevalence of tetralogy of Fallot, lower limb reduction defects, and trisomy 18, and a significantly lower birth prevalence of cleft palate, cleft lip with or without cleft palate, esophageal atresia/tracheoesophageal fistula, gastroschisis, and Down syndrome. Infants of Hispanic mothers, compared with infants of NH white mothers, had a significantly higher birth prevalence of anencephalus, spina bifida, encephalocele, gastroschisis, and Down syndrome, and a significantly lower birth prevalence of tetralogy of Fallot, hypoplastic left heart syndrome, cleft palate without cleft lip, and esophageal atresia/tracheoesophageal fistula. CONCLUSIONS: This study can be used to evaluate individual state surveillance data, and to help plan for public health care and educational needs. It also provides valuable data on racial/ethnic patterns of selected major birth defects.     

Rubella—Some Comments on the 1964-65 Epidemic in California

The rubella epidemic of 1964-1965 resulted in the birth of a group of children with defects of vision, of hearing or of the heart. In this study of cases known to five Los Angeles agencies, it was found that about half of those affected have more than one defect. Findings demonstrate a need for more sensitive communicable disease surveillance and for the development of services for the multiple handicapped child.     

Monitoring congenital rubella embryopathy

BACKGROUND: Currently, all developed countries include rubella vaccination in their immunization programs, targeting the complete elimination of congenital rubella syndrome (CRS). In the underdeveloped world, where this severely disabling condition still exists, only a few countries have implemented vaccination policies, and almost no data on their effectiveness or on prevalence rates are available. The aims of the present work were to search for the best phenotype to be used as a sentinel for CRS in a large series of malformed newborns and to propose a CRS surveillance system, based only on clinical data. METHODS: A total of 43 infants diagnosed as having CRS were obtained from 19,184 multimalformed infants, ascertained by the Latin-American Collaborative Study of Congenital Malformations, World Health Organization (WHO) Collaborating Centre for the Prevention of Birth Defects (ECLAMC), over 3,883,165 consecutive births, between 1982 and 2003. They were distributed by country and the most frequent birth defects were identified. From the 19,184 multimalformed infants, all cases presenting the birth defects identified were selected. The sensitivity, specificity, and likelihood ratio (LR) in detecting CRS were determined for these birth defects, alone and in combination. The sample size of multimalformed infants required to detect different levels of increase in the rate of CRS was determined for three sentinel phenotypes. RESULTS: The rate of CRS was highest in Brazil. Based on the best possible combination of sensitivity, specificity, and LR, the dyad comprising eye anomalies and congenital heart defects was shown to be the most appropriate sentinel, with the lowest sample size required, to detect CRS in neonates. CONCLUSIONS: A surveillance system for CRS, based on clinical data in newborns, is being proposed, in an attempt to monitor ongoing vaccination policies, aimed at eliminating CRS in developing countries.     

Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics

BACKGROUND: Although birth defects are a leading cause of death in infancy and early childhood, the proportion of all deaths to children with clinically diagnosed birth defects is not well documented. The study is intended to measure the proportion of all deaths to infants and children under age 10 occurring to children with birth defects and how and why this proportion differs from the proportion of deaths due to an underlying cause of congenital anomalies using standard mortality statistics. METHODS: A linked file of Michigan livebirths and deaths was combined with data from a comprehensive multisource birth defects registry of Michigan livebirths born during the years 1992 through 2000. The data were analyzed to determine the mortality rate for infants and children with birth defects and for children with no reported birth defect. Mortality risk ratios were calculated. The underlying causes of death for children with birth defects were also categorized and compared to cause- specific mortality rates for the general population. RESULTS: Congenital anomalies were the underlying cause of death for 17.8% of all infant deaths while infants with birth defects were 33.7% of all infant deaths in the study. Almost half of all Michigan deaths to children aged 1 to 2 were within the birth defects registry, though only 15.0% had an underlying cause of death of a congenital anomaly based upon standard mortality statistics. The mortality experience among children with birth defects was significantly higher than other children throughout the first 9 years of life, ranging from 4.6 for 5 year olds to 12.8 for children 1 to 2. Mortality risk ratios examined by cause of death for infants with birth defects were highest for other endocrine (28.1), other CNS (28.1), and heart (21.9) conditions. For children 1 through 9, the highest differential risk was seen for other perinatal conditions (39.0), other endocrine (29.7), other CNS (24.5), and heart (21.4). CONCLUSIONS: Childhood mortality analyses that incorporate birth defects registry data provide a more comprehensive picture of the full burden of birth defects on mortality in infant and children and can provide an effective mechanism for monitoring the survival and mortality risks of children with selected birth defects on a population basis.     

Use of prenatal diagnostic procedures in pregnancies affected with birth defects, Hawaii, 1986-2002

BACKGROUND: Information on the utilization of prenatal ultrasound (US), amniocentesis (AC), and chorionic villus sampling (CVS) in pregnancies affected by birth defects in the United States is limited. The intent of this study was to report on the utilization of these procedures in Hawaii. METHODS: Cases were all infants and fetuses of any pregnancy outcome with birth defects, included in a Hawaii birth defects registry, and delivered during 1986-2002. The rates of prenatal US, AC/CVS, and prenatal diagnosis were calculated. RESULTS: Prenatal US was performed in 76% of the cases and AC/CVS in 14% of the cases. Prenatal diagnosis of a birth defect was made in 16% of the cases. The prenatal US, AC/CVS, and prenatal diagnosis rates in 1998-2002 were 1.5, 1.5, and 1.7 times the rates in 1986-1991, respectively. Among all birth defects, the AC/CVS rate for women aged <35 years was 7% and for women aged > or =35 years was 48%. Among chromosomal abnormalities, the AC/CVS rate for women aged <35 years was 36% and for women aged > or =35 years was 66%. CONCLUSIONS: Only a fraction of the Hawaii birth defects cases was prenatally diagnosed. The rates for prenatal US, AC/CVS, and prenatal diagnosis among pregnancies affected by birth defects were higher in 1998-2002 than in 1986-1991. AC/CVS rates were lower for maternal age <35 years.     

Impact of Birth Seasonality on Dynamics of Acute Immunizing Infections in Sub-Saharan Africa

We analyze the impact of birth seasonality (seasonal oscillations in the birth rate) on the dynamics of acute, immunizing childhood infectious diseases. Previous research has explored the effect of human birth seasonality on infectious disease dynamics using parameters appropriate for the developed world. We build on this work by including in our analysis an extended range of baseline birth rates and amplitudes, which correspond to developing world settings. Additionally, our analysis accounts for seasonal forcing both in births and contact rates. We focus in particular on the dynamics of measles. In the absence of seasonal transmission rates or stochastic forcing, for typical measles epidemiological parameters, birth seasonality induces either annual or biennial epidemics. Changes in the magnitude of the birth fluctuations (birth amplitude) can induce significant changes in the size of the epidemic peaks, but have little impact on timing of disease epidemics within the year. In contrast, changes to the birth seasonality phase (location of the peak in birth amplitude within the year) significantly influence the timing of the epidemics. In the presence of seasonality in contact rates, at relatively low birth rates (20 per 1000), birth amplitude has little impact on the dynamics but does have an impact on the magnitude and timing of the epidemics. However, as the mean birth rate increases, both birth amplitude and phase play an important role in driving the dynamics of the epidemic. There are stronger effects at higher birth rates.     

Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study

BACKGROUND: Observational studies and clinical trials have suggested that periconceptional use of folic acid can reduce the risk of birth defects other than neural tube defects (NTDs). Using data reported by states to the National Birth Defects Prevention Network, we examined whether folic acid fortification might have decreased the prevalence of other specific birth defects. METHODS: For each of 16 birth defect categories selected for study, birth prevalence for two time periods was calculated with data submitted from a number of states in 1995-1996 ("pre-fortification") and 1999-2000 ("post-fortification"). Changes in birth prevalence between the two time periods were assessed by calculating prevalence ratios and 95% confidence intervals for each defect, and compared by maternal race/ethnicity and availability of prenatally diagnosed cases. RESULTS: We confirmed previously reported reductions in the birth prevalence of NTDs. In addition, we found modest, yet statistically significant, decreases in the birth prevalence for transposition of the great arteries(12%), cleft palate only (12%), pyloric stenosis (5%), upper limb reduction defects (11%), and omphalocele (21%). More substantial subgroup decreases were observed for renal agenesis among programs that conduct prenatal surveillance (28%), for common truncus among Hispanics (45%), and for upper limb reduction defects among Hispanics (44%). There were modest yet significant increases in the prevalence of obstructive genitourinary defects (12%) and Down syndrome (7%), but not among programs conducting prenatal surveillance for these defects. CONCLUSIONS: These results suggest some modest benefit from the folic acid fortification on the prevalence of a number of non-NTD birth defects.     

Birth defects prevalence among infants of Persian Gulf War veterans born in Hawaii, 1989-1993

BACKGROUND: Gulf War veterans (GWVs) have expressed concern about possible teratogenic exposures. However, epidemiologic studies on birth defects prevalence among their progeny have been limited to military hospitals, anomalies diagnosed among newborns, or self-reported data. To measure the prevalence of selected birth defects among infants of GWVs and nondeployed veterans (NDVs) in Hawaii, using birth defects surveillance records. METHODS: Personal identifiers of 684,645 GWVs and 1,587,102 NDVs and their families were matched against birth certificate records of 99,545 live births reported to the State of Hawaii Department of Health between 1989 and 1993 to identify births to military personnel. These births were matched with records from the Hawaii Birth Defects Program. RESULTS: A total of 17,182 military infants (3,717 GWV infants and 13,465 NDV infants) were identified. Of these, 367 infants (2.14/100 live births) were identified with one or more of 48 major birth defects diagnoses. The prevalence of the 48 birth defects were similar for GWV and NDV infants during the prewar and postwar periods, and among GWV infants who were conceived before and after the Gulf war. CONCLUSIONS: The results must be interpreted with caution because of the small number of affected infants in each birth defects category. This study demonstrated the feasibility of measuring birth defects prevalence among military infants through multiple data linkage. Further, it included live births to parents who had separated from the military, births in civilian hospitals, and birth defects diagnosed through the first year of life.     

The relation between small size for gestational age and the sex ratio of children with birth defects

BACKGROUND: Infants with birth defects are more likely to be born small for gestational age (SGA) than are other infants. This study describes a relation noted between the percentage SGA and the percentage male among children with various defect types. The data source was case records collected by the Metropolitan Atlanta Congenital Defects Program, a population-based, active surveillance system, during 1968 through 1998. METHODS: The study calculated the correlation between the percentage male and the percentage SGA for isolated cases of 44 different defect types for male-dominant and female-dominant defects separately. RESULTS: The correlation coefficient was -0.47 (P < 0.01) for male-dominant defects and 0.20 (P > 0.05) for female-dominant defects. Male-dominant defects were more likely to show less than 15% SGA and more likely to show the strongest risk differences by sex. CONCLUSIONS: These results are consistent with genetic causation of strongly skewed sex ratios, at least among male-dominant defects. Review of the literature suggests that defects with sex ratios closer to 1 are likely to have lower recurrence risks and therefore are less likely to be inherited than are other defects with skewed sex ratios. Sex ratios closer to 1 and a high percentage SGA may be markers of acquired or environmental birth defects.     

Use of CUSUM and Shewhart charts to monitor regional trends of birth defect reports in New York State

BACKGROUND: Cumulative sum (CUSUM) charts were originally developed for industrial quality control, but may be adapted for the surveillance of health outcome data, such as birth defects. The reported prevalence of birth defects can vary due to differences in case ascertainment, surveillance practices, or true changes in prevalence. We examined the utility of CUSUM and Shewhart charts for detect-ing changes in prevalence of two different birth defect groups. We chose obstructive renal defects because we expected an increase in reporting due to improved diagnosis. We chose oral clefts for comparison because we expected reporting to be unaffected by changes in diagnostic technologies. METHODS: Data from the New York State Congenital Malformations Registry from 1992-1999 were analyzed using self-starting binomial CUSUM and Shewhart charts for four regions of New York State. RESULTS: CUSUM charts show that reports of obstructive urinary defects have increased from 1992-1999 in all regions of New York State. Reports of oral clefts increased only on Long Island. CONCLUSIONS: The CUSUM method proved useful for identifying changes in birth defect reporting and was able to detect the expected increases in obstructive renal defects. The apparent increase is likely due to improvements in diagnostic imaging techniques. In contrast, we only detected an increase in oral clefts on Long Island, which may be related to under report-ing of cases in the earlier years. CUSUM charts are useful in detecting small, sustained increases in prevalences over time while Shewhart charts are easier to interpret and can detect large sharp increases.     

Birth defects in infants conceived by intracytoplasmic sperm injection: an alternative interpretation.

OBJECTIVE: To test the hypothesis that liveborn infants conceived by intracytoplasmic sperm injection are at an increased risk of having a major birth defect. DESIGN: Reclassification of the birth defects reported in infants born after intracytoplasmic sperm injection in Belgium and comparison with prevalence estimated in Western Australian population by means of same classification system. SETTING AND SUBJECTS: 420 liveborn infants who were conceived after intracytoplasmic sperm injection in Belgium and 100,454 liveborn infants in Western Australia delivered during the same period. MAIN OUTCOME MEASURES: Estimates of birth prevalence of birth defects and comparisons of odds ratios between cohort conceived after intracytoplasmic sperm injection and Western Australian infants. RESULTS: Infants born after intracytoplasmic sperm injection were twice as likely as Western Australian infants to have a major birth defect (odds ratio 2.03 (95% confidence interval 1.40 to 2.93); P = 0.0002) and nearly 50% more likely to have a minor defect (1.49 (0.48 to 4.66); P = 0.49). Secondary data-led analyses, to be interpreted with caution, found an excess of major cardiovascular defects (odds ratio 3.99), genitourinary defects (1.33), and gastrointestinal defects (1.84), in particular cleft palate (5.11) and diaphragmatic hernia (7.73). CONCLUSIONS: These results do not confirm the apparently reassuring results published by the Belgian researchers of intracytoplasmic sperm injection. Further research is clearly required. Meanwhile, doctors practising intracytoplasmic sperm injection should bear this alternative interpretation in mind when they counsel couples and obtain informed consent for the procedure.     

Measurement of child mortality in association with a multipurpose birth certificate programme in the Southern Highlands Province of Papua New Guinea.

A simple and inexpensive method for monitoring child mortality in association with birth registration was introduced into the Southern Highlands of Papua New Guinea. Eight thousand two hundred and one newborn infants were registered in 1988, approximately 77% of all children born in that year. The risk of death by age 2 was determined from reports given by the mother on the present status of a previously born child at the time of a recent delivery or during clinic registration of the current birth. This was 91 per 1000 for the province and corresponds to a risk of death by age 1 of 77/1000 by extrapolation using standard lifetables. This method was validated by comparison with a continuing demographic surveillance system covering 30,000 people in the western part of the province. The new birth certificate has been an incentive to increase supervised delivery rates and to generate a register that can be used to increase vaccination coverage.     

Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China

BACKGROUND : Previous studies inconsistently suggest that assisted reproduction technology (ART) may increase the risk of birth defects in children. METHOD(S) : Live birth infants, conceived by in vitro fertilization fresh embryo transfer (IVF), intracytoplasmic sperm injection fresh embryo transfer (ICSI), or frozen‐thawed embryo transfer (FET) in Reproductive Center of Tongji Hospital (Wuhan, China) between 1997 and 2008, were followed up at birth and after 3 years. Preterm pregnancy, multiple pregnancy, sex ratio (male/female), congenital malformation were compared. RESULT(S) : A total of 4,236 children were born after ART (IVF 2,543, ICSI 908, FET 785). Compared with IVF, the rate of preterm pregnancy and sex ratio in ICSI were lower (p < 0.05); the rate of multiple pregnancy in ICSI and FET were all lower than IVF (p < 0.05). Congenital defects were comparable in all groups at birth. In total, 2,908 children participated in the second follow‐up from 34 months to 60 months with an average of 40 months, and the cases of birth defects had doubled (3 years: 5.16%, birth: 2.22%). The birth defect rate in boys conceived through ICSI was significantly higher than the IVF group after 3‐year follow‐up (ICSI boys: 8.62%, IVF boys: 5.21% [p < 0.05]), even though there was no significant difference at birth. CONCLUSION(S) : Compared with IVF, FET may not increase risk of birth defects. Children conceived through ICSI, especially males, had higher rates of congenital malformations that were inapparent at birth. So longitudinal monitoring may provide insights into the risks of ART. Birth Defects Research (Part A) 97:744–749, 2013. 2013. © 2013 Wiley Periodicals, Inc.     

Trends in rates of multiple vascular disruption defects, Atlanta, 1968-1989: is there evidence of a cocaine teratogenic epidemic?

Research suggests that, perhaps through mechanisms initiated by vasoconstriction and leading to vessel thrombosis or embolism, cocaine causes vascular disruption defects, and that frequent cocaine use during early pregnancy could disrupt multiple organ systems in the fetus. We hypothesized that if cocaine is an important cause of multiple vascular disruption defects, a rising prevalence of cocaine use by mothers during pregnancy should be accompanied by rising rates of these defects in their offspring. Using data from the Metropolitan Atlanta Congenital Defects Program, we identified all infants born in Atlanta from 1968 through 1989 who had nonsyndromic, provisional vascular disruption defects affecting more than one organ system: 61 infants (78%) had gastrointestinal and genitourinary defects, 7 (9%) had gastrointestinal and abdominal wall defects, 2 (3%) had gastrointestinal and limb reduction defects, 2 (3%) had limb reduction and abdominal wall defects, 2 (3%) had central nervous system and gastrointestinal defects, 2 (3%) had genitourinary and limb reduction defects, 1 (1%) had genitourinary and abdominal wall defects, and 1 (1%) had central nervous system and genitourinary defects. The prevalence of Atlanta infants with more than one vascular disruption defect is 0.13 per 1,000 live births. Chi-square analysis for trends showed no increase in prevalence during the study period. Our data are from one of the first population-based studies in which trends for defects potentially caused by maternal cocaine use are examined; the results of our study show no significant change in the prevalence of multiple vascular disruption defects over time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue-engineered bone regeneration

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.     

Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment

BACKGROUND: Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects. METHODS: We evaluated surveillance data through 2003 on major birth defects from population-based registries from Europe, North America, and Australia. All included ascertainment of pregnancy terminations (where legal). Trends before and after policies or fortification were assessed via Poisson regression and were compared via rate ratios. RESULTS: Significant changes in trends were seen for NTDs in areas with fortification but not in areas with supplementation recommendations alone. For other major birth defects, there was an overall lack of major trend changes after recommendations or fortification. However, some significant declines were observed for select birth defects in individual areas. CONCLUSIONS: Recommendations alone remain an ineffective approach in translating the known protective effect of folic acid in population-wide decline in NTD rates. Fortification appears to be effective in reducing NTDs. The effect on other birth defects remains unclear.