Lead brownfields and birth defects in North Carolina 2003-2015: A cross-sectional case-control study.

BACKGROUND: Brownfields consist of abandoned and disused sites, spanning many former purposes. Brownfields represent a heterogenous yet ubiquitous exposure for many Americans, which may contain hazardous wastes and represent urban blight. Neonates and pregnant individuals are often sensitive to subtle environmental exposures. We evaluate if residential exposure to lead (Pb) brownfields is associated with birth defects. METHODS: Using North Carolina birth records from 2003 to 2015, we sampled 169,499 births within 10 km of a Pb brownfield with 3255 cardiovascular, central nervous, or external defects identified. Exposure was classified by binary specification of residing within 3 km of a Pb brownfield. We utilized multivariable logistic regression models adjusted for demographic covariates available from birth records and 2010 Census to estimate odds ratios (OR) and 95% confidence intervals (CI). Effect measure modification was assessed by inclusion of interaction terms and stratification for the potential modifiers of race/ethnicity and diabetes status. RESULTS: We observed positive associations between cardiovascular birth defects and residential proximity to Pb brownfields, OR (95%CI): 1.15 (1.04, 1.26), with suggestive positive associations for central nervous 1.16 (0.91, 1.47) and external defects 1.19 (0.88, 1.59). We did observe evidence of effect measure modification via likelihood ratio tests (LRT) for race/ethnicity for central nervous and external defect groups (LRT p values 0.08 and 0.02). We did observe modification by diabetes status for the cardiovascular group (LRT p value 0.08). CONCLUSIONS: Our results from this analysis indicate that residential proximity to Pb brownfields is associated with cardiovascular birth defects with suggestive associations for central nervous and external defects. In-depth analyses of individual defects and other contaminants or brownfield site functions may reveal additional novel associations.

Enhancing the Classification of Congenital Heart Defects for Outcome Association Studies in Birth Defects Registries.

INTRODUCTION: Traditional strategies for grouping congenital heart defects (CHDs) using birth defect registry data do not adequately address differences in expected clinical consequences between different combinations of CHDs. We report a lesion-specific classification system for birth defect registry-based outcome studies. METHODS: For Core Cardiac Lesion Outcome Classifications (C-CLOC) groups, common CHDs expected to have reasonable clinical homogeneity were defined. Criteria based on combinations of Centers for Disease and Control-modified British Pediatric Association (BPA) codes were defined for each C-CLOC group. To demonstrate proof of concept and retention of reasonable case counts within C-CLOC groups, Texas Birth Defect Registry data (1999-2017 deliveries) were used to compare case counts and neonatal mortality between traditional vs. C-CLOC classification approaches. RESULTS: C-CLOC defined 59 CHD groups among 62,262 infants with CHDs. Classifying cases into the single, mutually exclusive C-CLOC group reflecting the highest complexity CHD present reduced case counts among lower complexity lesions (e.g., 86.5% of cases with a common atrium BPA code were reclassified to a higher complexity group for a co-occurring CHD). As expected, C-CLOC groups had retained larger sample sizes (i.e., representing presumably better-powered analytic groups) compared to cases with only one CHD code and no occurring CHDs. DISCUSSION: This new CHD classification system for investigators using birth defect registry data, C-CLOC, is expected to balance clinical outcome homogeneity in analytic groups while maintaining sufficiently large case counts within categories, thus improving power for CHD-specific outcome association comparisons. Future outcome studies utilizing C-CLOC-based classifications are planned.

Tubal replacement of cervix for treatment of type II vaginal atresia complicated with cervical dysplasia: a case report.

Vaginal atresia is a rare obstructive disease of the reproductive tract. It is characterized by the absence or underdevelopment of the vaginal canal and results in various clinical manifestations. Hysterectomy can physically and mentally burden young female patients with a congenital cervix and complete vaginal atresia. This report presents a case of type II vaginal atresia complicated by cervical dysplasia in a female patient >10 years of age. Our team opted to preserve the patient's uterus, innovated a fallopian tube transplantation technique, and performed cervicovaginal reconstruction using natural channels instead of the cervical canal. The patient experienced menarche within the first 2 weeks postoperatively, and follow-up at 6 months revealed no abnormalities.

Patient with Herlyn-Werner-Wunderlich syndrome and endometriosis achieves successful full-term pregnancy (40 weeks and 6 days): a case report.

INTRODUCTION: Herlyn-Werner-Wunderlich syndrome , a rare Müllerian ducts congenital disease, is characterized by a diphtheritic uterus, blind hemivagina, and ipsilateral renal agenesis. Diagnosis is at young age by ultrasound and magnetic resonance imaging, and the prognosis is good. Usually, complications evolve endometriosis and secondary pelvic inflammation. CASE REPORT: A 40-year-old female patient, Brazilian, white, primigravida, diagnosed at 30 years with a didelphic uterus on ultrasound, and 4 years later, with a left ovarian endometrioma, multiple ovarian cysts, and left renal agenesis on magnetic resonance imaging. Subsequently, due to dyspareunia and a feeling of swelling, the patient underwent transvaginal ultrasound with bowel preparation, and a hematocolpos was found and Herlyn-Werner-Wunderlich syndrome was suspected; 10 years after the diagnosis she had a planned pregnancy. She presented frequent contractions following the 15th week of pregnancy and fortunately there were no complications or premature labor. Labor was inducted at 40 weeks and 6 days without progress and a cesarean section was indicated and performed without complications. Herlyn-Werner-Wunderlich syndrome often goes unnoticed, leading to inadequate treatment. Individuals with Herlyn-Werner-Wunderlich syndrome commonly face fertility issues, such as high miscarriage rate (21-33%), and obstetric complications, such as spontaneous abortions (40% risk), intrauterine growth restriction, postpartum hemorrhage, increased fetal mortality, preterm delivery (21-29%), and elevated rates of cesarean sections. In addition, there is higher susceptibility of developing endometriosis, especially with hemivaginal obstruction, and pelvic adhesions. CONCLUSION: Early diagnosis enables timely treatment and, consequently, fewer complications. Still, when these factors are absent, vaginal birth may still be possible. The true prevalence and incidence of complications related to Herlyn-Werner-Wunderlich syndrome are still unknown.

Population-based prevalence of congenital defects in a routine sentinel site-based surveillance system in the Western Cape, South Africa.

BACKGROUND: Lack of data on the burden and scope of congenital disorders (CDs) in South Africa undermines resource allocation and limits the ability to detect signals from potentially teratogenic pregnancy exposures. METHODS: We used routine electronic data in the Western Cape Pregnancy Exposure Registry (PER) to determine the overall and individual prevalence of CD identified on neonatal surface examination at birth in the Western Cape, South Africa, 2016-2022. CD was confirmed by record review. The contribution of late (≤24 months) and antenatal diagnoses was assessed. We compared demographic and obstetric characteristics between women with/without pregnancies affected by CD. RESULTS: Women with a viable pregnancy (>22 weeks gestation; birth weight ≥ 500 g) (n = 32,494) were included. Of 1106 potential CD identified, 56.1% were confirmed on folder review. When internal and minor CD were excluded the prevalence of major CD identified on surface examination at birth was 7.2/1000 births. When missed/late diagnoses on examination (16.8%) and ultrasound (6.8%) were included, the prevalence was 9.2/1000 births: 8.9/1000 livebirths and 21.5/1000 stillbirths. The PER did not detect 21.5% of major CD visible at birth. Older maternal age and diabetes mellitus were associated with an increased prevalence of CD. Women living with/without HIV (or the timing of antiretroviral therapy, before/after conception), hypertension or obesity did not significantly affect prevalence of CD. CONCLUSIONS: A surveillance system based on routine data successfully determined the prevalence of major CD identified on surface examination at birth at rates slightly higher than in equivalent studies. Overall rates, modeled at ~2%, are likely underestimated. Strengthening routine neonatal examination and clinical record-keeping could improve CD ascertainment.

Qualitative Pilot Study: Longitudinal Perspectives From People Who Had Second Trimester Abortions for Fetal Anomaly.

BACKGROUND: We investigated patient experience with abortion for fetal anomaly, about which little is known. METHODS: This qualitative, longitudinal pilot study surveyed 7 patients twice after abortion for fetal anomaly, initially 4 to 5 days after the abortion and a follow-up 3 months post-abortion, at a single Wisconsin hospital from July 2012 to February 2014. RESULTS: Patients indicated that having a choice to have an abortion and choose the modality is imperative, and they remained certain in their decision-making over time. They also described initially strong, then lacking, social support; processed grief; and identified resource constraints. DISCUSSION: Patients emphasized the importance of having the choice to choose abortion and the abortion modality, remaining confident in their decision-making over time. This qualitative pilot study provides areas for future intervention to improve care for people undergoing abortion for fetal anomaly.

Birth defects among offspring of California firefighters, 2007-2019.

PURPOSE: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. METHODS: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. RESULTS: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. CONCLUSIONS: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Birth defects in a rural province in Papua New Guinea.

BACKGROUND: Globally, birth defects are the fourth most common cause of neonatal mortality. They cause substantial morbidity, and often long-term disability. Despite this, the impact of birth defects on public health has received little attention in low- and middle-income countries. AIMS: To report the types, incidence and geographic distribution of birth defects in the East New Britain Province of Papua New Guinea. METHODS: Data were collected over 3 years on newborns with birth defects seen at Rabaul Hospital, born anywhere in the province. Each affected newborn was examined, the anomaly diagnosed and classified. The exact home location was recorded to understand geospatial distribution. To calculate incidence, data were collected on all newborns with a congenital anomaly in a cohort of 2000 consecutive live births at Rabaul Hospital in 2019. RESULTS: Over 3 years, 2018-2020, 137 newborns with birth defects were identified, born in any part of the province. Congenital heart defects, hydrocephalus, microcephaly, craniofacial anomalies, imperforate anus, trachea-oesophageal fistula and diaphragmatic hernia were the most common anomalies. Eight cases of Down syndrome and other chromosomal anomalies were identified. The incidence in 2019 was 14 per 1000 live births. Geographic mapping showed the highest number of cases in the region on the Gazelle Peninsula, the area around the active volcanos. CONCLUSIONS: This study provides insights into the incidence and types of birth defects in a rural island province and showed it was possible to map geospatial distribution to further explore epidemiology.

Clinical evaluation of temporal bone anatomical abnormalities and surgical method selection in patients with congenital aural atresia.

OBJECTIVES: To analyze anatomic variations of the temporal bone in congenital aural atresia (CAA) and their correlation with the Jahrsdoerfer score, in order to guide clinical selection of surgical treatment methods. MATERIAL AND METHODS: We retrospectively studied 53 patients (72 ears) with unilateral or bilateral CAA, including 34 ears with normal hearing as controls. Audiological and imaging data were collected and analyzed. We evaluated the Jahrsdoerfer score and anatomical variations, including tegmen mastoideum position, anterior sigmoid sinus displacement, and elevated jugular bulb. RESULTS: The average air conduction hearing threshold (PTA4) ranged from 0.5 to 4 kHz was 65.48 ± 8.19 dBHL, with an average Jahrsdoerfer score of 4.93 ± 2.78. In CAA group, there was a higher prevalence and severity of anterior sigmoid sinus and low position of the tegmen mastoideum (P < 0.01). However, there was no significant difference in incidence rates among groups with high jugular bulb (P > 0.05). Anterior sigmoid sinus and high jugular bulb showed no correlation with the Jahrsdoerfer score, while the low position of the tegmen mastoideum had a weak correlation. The Jahrsdoerfer score did not adequately predict temporal bone anatomical abnormalities in CAA patients. CONCLUSION: CAA exhibit a higher incidence and greater severity of temporal bone anatomical abnormalities compared to the control group, and the Jahrsdoerfer score inadequately assesses these abnormalities. Anomalies like low position of the tegmen mastoideum, anterior sigmoid sinus, and high jugular bulb should also be considered as independent factors influencing surgical decisions for atresiaplasty.

COVID-19 Vaccination in the First Trimester and Major Structural Birth Defects Among Live Births.

Importance: COVID-19 vaccination is recommended throughout pregnancy to prevent pregnancy complications and adverse birth outcomes associated with COVID-19 disease. To date, data on birth defects after first-trimester vaccination are limited. Objective: To evaluate the associated risks for selected major structural birth defects among live-born infants after first-trimester receipt of a messenger RNA (mRNA) COVID-19 vaccine. Design, Setting, and Participants: This was a retrospective cohort study of singleton pregnancies with estimated last menstrual period (LMP) between September 13, 2020, and April 3, 2021, and ending in live birth from March 5, 2021, to January 25, 2022. Included were data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Exposures: Receipt of 1 or 2 mRNA COVID-19 vaccine doses in the first trimester, as part of the primary series. Main Outcomes and Measures: Selected major structural birth defects among live-born infants, identified from electronic health data using validated algorithms, with neural tube defects confirmed via medical record review. Results: Among 42 156 eligible pregnancies (mean [SD] maternal age, 30.9 [5.0] years) 7632 (18.1%) received an mRNA COVID-19 vaccine in the first trimester. Of 34 524 pregnancies without a first-trimester COVID-19 vaccination, 2045 (5.9%) were vaccinated before pregnancy, 13 494 (39.1%) during the second or third trimester, and 18 985 (55.0%) were unvaccinated before or during pregnancy. Compared with pregnant people unvaccinated in the first trimester, those vaccinated in the first trimester were older (mean [SD] age, 32.3 [4.5] years vs 30.6 [5.1] years) and differed by LMP date. After applying stabilized inverse probability weighting, differences in baseline characteristics between vaccinated and unvaccinated pregnant persons in the first trimester were negligible (standardized mean difference <0.20). Selected major structural birth defects occurred in 113 infants (1.48%) after first-trimester mRNA COVID-19 vaccination and in 488 infants (1.41%) without first-trimester vaccine exposure; the adjusted prevalence ratio was 1.02 (95% CI, 0.78-1.33). In secondary analyses, with major structural birth defect outcomes grouped by organ system, no significant differences between infants vaccinated or unvaccinated in the first trimester were identified. Conclusions and Relevance: In this multisite cohort study, among live-born infants, first-trimester mRNA COVID-19 vaccine exposure was not associated with an increased risk for selected major structural birth defects.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

Exploring potential causal links between air pollutants and congenital malformations: A two-sample Mendelian Randomization study.

Observational studies have suggested an association between air pollutants and congenital malformations; however, conclusions are inconsistent and the causal associations have not been elucidated. In this study, based on publicly available genetic data, a two-sample Mendelian randomization (MR) was applied to explore the associations between particulate matter 2.5 (PM2.5), NOX, NO2 levels and 11 congenital malformations. Inverse variance weighted (IVW), MR-Egger and weighted median were used as analytical methods, with IVW being the main method. A series of sensitivity analyses were used to verify the robustness of the results. For significant associations, multivariable MR (MVMR) was utilized to explore possible mediating effects. The IVW results showed that PM2.5 was associated with congenital malformations of digestive system (OR = 7.72, 95 %CI = 2.33-25.54, P = 8.11E-4) and multiple systems (OR = 8.63, 95 %CI = 1.02-73.43, P = 0.048) risks; NOX was associated with circulatory system (OR = 4.65, 95 %CI = 1.15-18.86, P = 0.031) and cardiac septal defects (OR = 14.09, 95 %CI = 1.62-122.59, P = 0.017) risks; NO2 was correlated with digestive system (OR = 27.12, 95 %CI = 1.81-407.07, P = 0.017) and cardiac septal defects (OR = 22.57, 95 %CI = 2.50-203.45, P = 0.005) risks. Further MVMR analyses suggest that there may be interactions in the effects of these air pollutants on congenital malformations. In conclusion, this study demonstrated a causal association between air pollution and congenital malformations from a genetic perspective.

A case of Herlyn-Werner-Wunderlich syndrome with exacerbation of hematometra after adnexectomy.

A 27-year-old nulliparous woman presented with a feeling of fullness in the lower abdomen and abdominal pain. A left ovarian tumor, uterus didelphys, left renal agenesis, and left vaginal atresia were observed on imaging. The ovarian tumor was presumed to have caused the abdominal pain, and an abdominal left adnexectomy was performed. After 3 months, she reported severe lower abdominal pain during menstruation. Transvaginal ultrasonography revealed uterine enlargement. After 17 days, the patient presented with abdominal pain and fever. She was diagnosed with peritonitis due to infection and left uterine hematometra. Because she did not improve with antibiotic treatment, left laparoscopic hysterectomy was performed. Subsequently, she did not experience the lower abdominal pain. Appropriate diagnosis and treatment based on the morphology of the reproductive tract and symptoms must be considered in patients with Herlyn-Werner-Wunderlich syndrome. Treatment must permit the outflow of menstrual blood.

Fetal deaths from birth defects in Hunan Province, China, 2016-2020.

To describe the fetal death rate of birth defects (including a broad range of specific defects) and to explore the relationship between fetal deaths from birth defects and a broad range of demographic characteristics. Data was derived from the birth defects surveillance system in Hunan Province, China, 2016-2020. Fetal death refers to the intrauterine death of a fetus at any time during the pregnancy, including medical termination of pregnancy. Fetal death rate is the number of fetal deaths per 100 births (including live births and fetal deaths) in a specified group (unit: %). The fetal death rate of birth defects with 95% confidence intervals (CI) was calculated by the log-binomial method. Crude odds ratios (ORs) were calculated to examine the relationship between each demographic characteristic and fetal deaths from birth defects. This study included 847,755 births, and 23,420 birth defects were identified. A total of 11,955 fetal deaths from birth defects were identified, with a fetal death rate of 51.05% (95% CI 50.13-51.96). 15.78% (1887 cases) of fetal deaths from birth defects were at a gestational age of < 20 weeks, 59.05% (7059 cases) were at a gestational age of 20-27 weeks, and 25.17% (3009 cases) were at a gestational age of ≥ 28 weeks. Fetal death rate of birth defects was higher in females than in males (OR = 1.25, 95% CI 1.18-1.32), in rural than in urban areas (OR = 1.43, 95% CI 1.36-1.50), in maternal age 20-24 years (OR = 1.35, 95% CI 1.25-1.47), and ≥ 35 years (OR = 1.19, 95% CI 1.11-1.29) compared to maternal age of 25-29 years, in diagnosed by chromosomal analysis than ultrasound (OR = 6.24, 95% CI 5.15-7.55), and lower in multiple births than in singletons (OR = 0.41, 95% CI 0.36-0.47). The fetal death rate of birth defects increased with the number of previous pregnancies (χ2trend = 49.28, P < 0.01), and decreased with the number of previous deliveries (χ2trend = 4318.91, P < 0.01). Many fetal deaths were associated with birth defects. We found several demographic characteristics associated with fetal deaths from birth defects, which may be related to the severity of the birth defects, economic and medical conditions, and parental attitudes toward birth defects.

Newborn screening analytes and structural birth defects among 27,000 newborns.

BACKGROUND: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects. METHODS: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis. FINDINGS: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes). CONCLUSIONS: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects.

What are they considering when they face a fetus with birth defects? A qualitative study on ethical attitudes of health professionals in China.

BACKGROUND: Birth defects are the leading cause of mortality in newborn babies and children under five years old. In response, the Chinese government has implemented a three-tiered prevention strategy, which has brought ethical concerns about fetuses with birth defects. This study aims to explore the attitudes toward fetuses with birth defects among health professionals engaged in maternal and child health services. METHODS: A qualitative study was conducted among 13 health professionals engaged in maternal and child health services in Hunan Province, China. The questions were designed to elicit the participants' work experience and attitudes toward fetuses with birth defects. The data were collected through in-depth semi-structured interviews, and NVivo 12 was used for data coding and analysis. A thematic analysis approach was employed following the SRQR checklist. RESULTS: Five themes and 13 attributes were generated regarding health professionals' perspectives on fetuses with birth defects. The five themes included: (1) severity and curability of diseases (two attributes), (2) family relations (four attributes), (3) medical assessments (two attributes), (4) social situations (three attributes), (5) self-value orientations (three attributes). The findings showed that the majority of health professionals held the view that a fetus with a curable disease could be born, whereas a fetus with severe disability and teratogenesis should be terminated. Twelve out of the 13 health professionals believed that parents should be the decision-makers, while only one thought that the family should make a decision together. CONCLUSIONS: Attitudes toward birth defects were influenced by various factors, indicating the complexity of real-world cases identified in this study. The findings highlight the dilemmas faced by both families and health professionals regarding birth defects. Adequate medical knowledge and support from society are crucial to inform decision-making among family members. Additionally, standardized norms and policies for birth defects are needed. Establishing an ethics committee for prenatal diagnosis is necessary to address current ethical issues in this field.

Moderate altitude as a risk factor for isolated congenital malformations. Results from a case-control multicenter-multiregional study.

BACKGROUND: Living in high-altitude regions has been associated with a higher prevalence of some birth defects. Moderate altitudes (1500-2500 m) have been associated with some congenital heart diseases and low birth weight. However, no studies have been conducted for other isolated congenital malformations. OBJECTIVES: To estimate the prevalence at birth of isolated congenital malformations in low and moderate altitudes and to determine if moderate altitudes are a risk factor, such as high altitudes, for isolated congenital malformations adjusted for other factors. METHODS: The study consisted of a case-control multicenter-multiregional study of 13 isolated congenital malformations. Cases included live births with isolated congenital malformations and controls at low (10-1433 m) and moderate altitudes (1511-2426 m) from a Mexican registry from January 1978 to December 2019. Prevalence per 10,000 (95% CI) per altitude group was estimated. We performed unadjusted and adjusted logistic regression models (adjusted for maternal age, parity, malformed relatives, socioeconomic level, and maternal diabetes) for each isolated congenital malformation. RESULTS: Hydrocephaly and microtia had a higher at-birth prevalence, and spina bifida, preauricular tag, and gastroschisis showed a lower at-birth prevalence in moderate altitudes. Moderate altitudes were a risk factor for hydrocephaly (aOR 1.39), microtia (aOR 1.60), cleft-lip-palate (aOR 1.27), and polydactyly (aOR 1.32) and a protective effect for spina bifida (aOR 0.87) compared with low altitudes. CONCLUSIONS: Our findings provide evidence that moderate altitudes as higher altitudes are an associated risk or protective factor to some isolated congenital malformations, suggesting a possible gradient effect.

[Call for attention to the prevention of perinatal death attributed to birth defect].

Birth defect and perinatal death are major public issues threatening the health of women and children in China. However, perinatal death attributed to birth defects has not yet received sufficient attention. To minimize the occurrence of perinatal death caused by birth defects, this review article deeply analyzed the current status of epidemiology, clinical, and basic research on perinatal death attributed to birth defects both domestically and internationally, and proposed to encourage the conduct of national research on perinatal causes. We should also pay attention to the application of the perinatal cause of death classification system, and focus on accurate diagnosis and the three-level prevention and control of perinatal death attributed to birth defect.