Major Congenital Anomalies Research Articles

Elevated risk for developmental disabilities in children with congenital heart defects.

This study examined risk for developmental disabilities in preschool-aged children with a congenital heart defect (CHD) at the population level. Statewide birth, birth defects, and preschool developmental disability records were integrated. The final sample included 1,966,585 children (51.0% male). Children were grouped by type(s) of CHD: critical CHD, noncritical CHD, atrial septal defect, or no major birth defects (groups were mutually exclusive). Children with a CHD (any type) were at increased risk for developmental disability (any type) (RR 2.08, 95% CI 2.03-2.14, P < .001). Children in the critical CHD, noncritical CHD, and atrial septal defect groups were at increased risk for developmental delay, intellectual disability, language impairment, other health impairment, and any disability. Children in the atrial septal defect group were at increased risk for autism spectrum disorder and speech impairment. For all CHD groups, risk was greatest for other health impairment and intellectual disability. Increased risk for developmental disabilities was identified for children with less severe CHDs as well as for children with more severe (critical) CHDs. All children with CHDs should be closely monitored so that appropriate interventions can be initiated as early as possible to maximize learning outcomes.

Knowledge, Attitude and Practices Among Mothers of Infants Regarding Breastfeeding.

This study aims at understanding the level of knowledge, attitude, and practice of breastfeeding among mothers and the factors associated with good knowledge about breastfeeding. A cross-sectional study among 251 mothers of infants admitted in the pediatric wards of SAT Hospital, Thiruvananthapuram was conducted during November-December 2019. The mothers of infants born between 37 and 42 weeks of gestation and without major birth defects were included in the study. The data were entered into an MS Excel sheet and analyzed using Statistical Package of Social Sciences version 26.0. Significance of association was tested using Chi-square test and multivariate analysis was done using binary logistic regression test. The mean age of the participants was 26.25 (SD 4) years. On multivariable analysis, higher education and older age were found to be significantly associated with good knowledge. Independent sample T-Test results show that there was a statistically significant difference between the mean age of mothers with good knowledge (26.4(±4), 25.14(±3.7)), p-0.015 and statistically significant association was found between the mean attitude scores (34.07(5.58)) with current breastfeeding practices (p=0.002). Chi-square test shows that exclusive breastfeeding was significantly associated with the mother's age (p=0.006); 64.2% of women practicing exclusive breastfeeding were less than 25 years of age. This study also demonstrated a significant association between the initiation of breastfeeding within an hour and exclusive breastfeeding (p=0.003). This study shows that mothers with higher age and higher educational qualifications were significantly associated with good knowledge about breastfeeding. Even though mothers have good knowledge, nearly half the mothers only exclusively breastfeed their infants for six months. Improving the educational qualification of women and increasing awareness about the benefits of breastfeeding among young women will promote breastfeeding practices.

Integrated care in cardiac intensive care unit for noncardiovascular complications in children after open-heart surgery: A comprehensive review

Abstract Congenital heart defects (CHDs), the most common major birth defects, undergo effective surgical care in the last decade, enhancing survival. After heart surgery, mechanical, infectious, and noninfectious causes induce pediatric pulmonary problems. Necrotizing enterocolitis and feeding intolerance are frequent digestive issues. Diuretics relieve fluid excess, but early dialysis may help in cardiac intensive care unit (CICU) patients. Cumulative insulin dosages improve postoperative hyperglycemia. Noncardiac organ system problems are common in current pediatric cardiac intensive care units including seizures needing anti-epileptics. While, managing the patients in CICU, one must consider noncardiac organ system integrity and function.

Trends in Procedural Closure of the Patent Ductus Arteriosus among Infants Born at 22 to 30 Weeks’ Gestation

To describe recent trend in procedural closure of the patent ductus arteriosus (PDA) among premature infants and compare the clinical characteristics of infants receiving surgical vs transcatheter closure. We conducted a descriptive, retrospective cohort study of preterm infants born between 220/7 and 296/7weeks' gestation from 2014 through 2021. Infants were identified from the Pediatrix Clinical Data Warehouse. We excluded infants with any major congenital anomaly. We identified all preterm infants with a PDA and all those who underwent procedural closure (surgical ligation or transcatheter occlusion) and compared changes over time using ANOVA for continuous variables and the Cochran-Armitage trend test to evaluate time-related changes in proportions. The study cohort included 64 580 infants, of whom 24 028 (37.2%) were diagnosed with a PDA. The number of infants receiving any procedural closure of the PDA decreased from 371 (4.4%) in 2014 to 144 (1.9%) in 2021. During the same period, number of surgical ligations decreased from 369 (4.36%) to 64 (0.84%), and the number of transcatheter occlusions increased from 2 (0.02%) to 80 (1.05% p for all < 0.001). The median age at time of surgical ligation increased from 25 days (10th and 90th percentile, 10, 61) to 31days (10th and 90th percentile, 16, 66), and the median age of transcatheter occlusion decreased from 103days (10th and 90th percentile, 32, 150) to 43days (10th and 90th percentile, 22, 91). There was a decrease in surgical closure and an increase in transcatheter occlusion of the PDA in infants born at 22-30weeks' gestation from 2014 to 2021. Despite the decline in overall procedural closure, the rate of transcatheter occlusion surpassed surgical ligation by 2021. Narrowing differences in the median age and weight at closure suggest increasing overlap in the types of infants who received each type of procedural closure.

An expanded view of infertility: The challenge of the changing profiling of major birth defects in China.

Over the past two decades, China has experienced a significant decline in birth rates, accompanied by a decrease in fertility and changes in major congenital defects. The development of assisted reproductive technology (ART) has brought hope to individuals facing infertility. However, some issues related to reproductive health and congenital defects have arisen. The reasons for the changing profiling of birth defects and the relationship between the decline in fertility and ART need to be further investigated. Lifestyle factors such as nutritional supplementation need to be altered to protect reproductive capacity. Birth defects, such as congenital heart defects and hypospadias, may serve as a signal for understanding the decline in fertility. To improve fertility, the factors contributing to it need to be identified, vital genetic and medical technologies need to be introduced, and environmental interventions, such as nutritional changes, need to be implemented.

Functional measures on PEDI are associated with BSID-3 scales at 2 years, following neonatal surgery

BackgroundNeonates requiring early surgical intervention for major non-cardiac congenital anomalies are at high risk of adverse neurodevelopmental outcomes. Early recognition of potential neuro-developmental delay is critical to facilitate access to early childhood intervention services and therefore maximise the functional capabilities of these children. AimsThis study aims to compare Bayley's Scales of Infant and Toddler Development (BSID-3) and the Paediatric Evaluation of Disability Inventory (PEDI) as early screening tools in predicting neuro-developmental disability across multiple domains. In addition, it looks at determining which pre, peri and post-operative risk factors lend themselves to more adverse outcomes. Study designRetrospective cohort study. SubjectsNeonates requiring surgical intervention at the Royal Children's Hospital from 2012 to 2018 who subsequently underwent neurodevelopmental assessment at 2 years of age. Outcome measuresThe main outcome was the relationship between performance on the PEDI compared with the BSID-3, in 2-year-olds following neonatal surgery. ResultsParent -reported functional measures across all domains on PEDI strongly related to the more formal measures of cognition, language, and motor development assessed on BSID-3 (p < 0.05). ConclusionsThe questionnaire-based PEDI tool could be considered a reliable replacement to the formal Bayley (BSID-3) scale in low-risk infants and provide a more accessible means of assessment where there are deficiencies in availability of suitably trained clinicians or limited resource centres.

Association of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with aneuploidy pregnancy susceptibility

BackgroundAneuploidy pregnancy is a severe major birth defect and causes about 50% spontaneous miscarriages with unknown etiology. To date, only a few epidemiological studies with small sample sizes have investigated the risk factors for aneuploidy pregnancy. TP53, MDM2, and miR-34b/c genes are implicated in tumorigenesis with aneuploidy, yet the function of their polymorphisms in aneuploidy pregnancy susceptibility needs to be clarified.ObjectiveTo elucidate the association of TP53 rs1042522 G > C, MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C specific polymorphisms with aneuploidy pregnancy.MethodsIn the retrospective case-control study, 330 aneuploidies pregnancy women and 813 normal pregnancy controls were recruited between January 2018 and April 2022 at the First People’s Hospital of Yunnan Province, Kunming, China. Three functional polymorphisms, the TP53 rs1042522 G > C (Arg72Pro), MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C, were genotyped using the snapshot method.ResultsThe frequency distribution of three genotypic variants was not different between case and control pregnant women and was similar to with Hardy-Weinberg Equilibrium (HWE). However, in the younger subgroup (less than 35 years old), a significant difference was detected in allele and recessive model (p = 0.01). In the advanced age subgroup (more than or equal to 35 years old), G of MDM2 rs2279744 T > G revealed a significantly higher frequency in cases than controls (p = 0.045), and miR-34b/c rs4938723 T > C revealed a significant difference under the dominant model (p = 0.03), but no significant differences were observed in other models and in both younger and older subgroup (p > 0.05, respectively). These results suggest that individual polymorphisms were not associated with aneuploidy pregnancy, combined with age, they may serve as a risk factor for aneuploidy pregnancy.ConclusionCombination of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with maternal age may be related to aneuploidy pregnancy susceptibility. These findings might elaborate on the genetic etiology of aneuploidy pregnancy.

Morbidity and Mortality of Very-Low-Birthweight Twin Infants according to Their Sex and the Sex of the Co-Twin: A Retrospective Cohort Study

Introduction: The concept of male disadvantage regarding the prognosis of premature newborns was introduced more than half a century ago, and it has been corroborated over time. However, the influence of the sex of one twin on the outcomes of the other has yielded contradictory results. Objective: The aim of the study was to determine if, in twin pregnancies of VLBW infants, the outcomes of one twin are modified by the sex of the co-twin. Methods: A multicentre retrospective study of a cohort of infants admitted to the collaborating units of the Spanish SEN1500 neonatal network was conducted. Liveborn VLBW twin infants, from 23+0 to 31+6 weeks of gestational age (GA), admitted from 2011 to 2020 were included. Outborn patients, infants with major congenital anomalies, and cases with only one twin admitted were excluded. The main outcomes were survival until first hospital discharge, survival without moderate or severe bronchopulmonary dysplasia (BPD), survival without major brain damage (MBD), and survival without major morbidity. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were calculated. Results: 2,111 twin pairs were included. Male infants exhibited worse outcomes than females (IRR; 95% CI) regarding survival (0.96; 0.94, 0.98), survival without moderate or severe BPD (0.89; 0.86, 0.93), survival without MBD (0.94; 0.91, 0.97), and survival without major morbidity (0.87; 0.81, 0.93). Differences disappeared when the co-twin was a female infant: survival (1.00; 0.97, 1.03), survival without moderate or severe BPD (0.96; 0.91, 1.01), survival without MBD (0.99; 0.95, 1.04), and survival without major morbidity (0.94; 0.85, 1.03). Results for female infants did not change significantly with co-twin sex. Conclusions: Among VLBW twins from 23+0 to 31+6 weeks of GA, male infants have higher risk of morbidity and mortality overall. In cases of pregnancies with different-sex foetuses, males seem to improve their results, while these do not change for females. The underlying mechanism of this influence deserves further investigation.

Cancer risk in the siblings of individuals with major birth defects: a large Nordic population-based case-control study.

Individuals with major birth defects are at increased risk of developing cancer, indicating a common aetiology. However, whether the siblings of individuals with birth defects are also at an increased risk of cancer is unclear. We used nationwide health registries in four Nordic countries and conducted a nested case-control study. We included 40 538 cancer cases (aged 0-46 years) and 481 945 population controls (matched by birth year and country), born between 1967 and 2014. The relative risk of cancer among individuals whose siblings had birth defects was computed with odds ratios (OR) and 95% confidence intervals (CIs), using logistic regression models. In the total study population (aged 0-46 years), we observed no overall difference in cancer risk between individuals whose siblings had birth defects and those who had unaffected siblings (OR 1.02; 95% CI 0.97-1.08); however, the risk of lymphoid and haematopoietic malignancies was elevated (1.16; 1.05-1.28). The overall risk of childhood cancer (0-19 years) was increased for siblings of individuals who had birth defects (1.09; 1.00-1.19), which was mainly driven by lymphoma (1.35; 1.09-1.66), neuroblastoma (1.51; 1.11-2.05) and renal carcinoma (5.03; 1.73-14.6). The risk of cancer also increased with the number of siblings with birth defects (Ptrend = 0.008). Overall risk of cancer among individuals (aged 0-46 years) whose siblings had birth defects was not elevated, but the risk of childhood cancer (ages 0-19 years) was increased. Our novel findings are consistent with the common aetiologies of birth defects and cancer, such as shared genetic predisposition and environmental factors.

Educational achievement of children with selected major congenital anomalies and associated factors: a Finnish registry-based study.

Children with major congenital anomalies may be at risk of poor educational outcomes. We aimed to evaluate the educational achievement of children born with major congenital anomalies compared with children without major congenital anomalies in relation to sociodemographic factors. We performed a registry-based study including 401544 children in Finland, graduates of the compulsory school who applied to secondary education. We used health data from the Finnish Register of Congenital Malformations for children born from 1995 to 2002 linked with education data from the Finnish Ministry of Education and Culture. We used generalized linear regression to compare the mean grade differences of children with specific major congenital anomalies and 'All anomalies' subgroup (major congenital anomalies, chromosomal syndromes, and multiple anomalies) with reference children. Children with major congenital anomalies were less likely to apply for further education than reference children (88.0% vs. 96.8%; odds ratio = 4.13; 95% confidence interval, 3.92-4.36). For most non-chromosomal congenital anomalies, children born with congenital anomalies had similar educational achievement to the reference children. For the 'All anomalies' subgroup, children with congenital anomalies had lower educational achievement than reference children. Among children with congenital anomalies, male sex, lower maternal educational levels and younger maternal age were associated with lower educational achievement. For children applying to further education, most non-chromosomal congenital anomalies were not associated with lower educational achievement. Nevertheless, efforts are needed to improve educational achievement in children with major congenital anomalies associated with maternal sociodemographic background.

Daltveit DS, Klungsøyr K, Engeland A, et al. Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults[J]. BMJ, 2020, 371:m4060. DOI: 10.1136/bmj.m4060.

Daltveit DS, Klungsøyr K, Engeland A, et al. Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults[J]. BMJ, 2020, 371:m4060. DOI: 10.1136/bmj.m4060.

Artificial oocyte activation with Ca2+ ionophore improves reproductive outcomes in patients with fertilization failure and poor embryo development in previous ICSI cycles.

Does artificial oocyte activation (AOA) by a calcium ionophore (ionomycin) improve the previous fertilization failure or poor embryo development of intracytoplasmic sperm injection (ICSI) account for male factor infertility or other infertility causes? This retrospective study involved 114 patients receiving ICSI-AOA in Shanghai First Maternity and Infant Hospital with previous ICSI fertilization failure or poor embryo development. The previous ICSI cycles of the same patients without AOA served as the control group. The fertilization rates, cleavage rates, transferable embryo rates and blastocyst formation rates of the two groups were compared. Additionally, the clinical pregnancy, implantation rate and live birth rates were also compared to assess the efficiency and safety of AOA. Furthermore, two subgroup analyses were performed in this study based on the cause of infertility and the reason for AOA. The fertilization rate, embryonic development potential and clinical outcome were compared among groups. Among 114 ICSI-AOA cycles, the fertilization rate, top-quality embryo rate, implantation rate, clinical pregnancy per patient and live birth rate per patient were improved significantly compared with previous ICSI cycles (p<0.05 to P< 0.001), and the miscarriage rate in the AOA group was significantly lower than that of the control group (p<0.001). In the AOA subgroups based on the cause of infertility, the fertilization rates of each subgroup were significantly improved compared with previous control cycles except for the mixed factor infertility subgroup (p<0.05 to p<0.001). In the AOA subgroups based on the reason for AOA, the fertilization rates of each subgroup were significantly increased compared with those in their previous ICSI cycle without AOA (p<0.001); however, there was no significant difference in the top-quality embryo rate. No significant improvement was found in the implantation rates and the clinical pregnancy rate in each subgroup except for the poor embryo development subgroup. In the 114 AOA cycles, 35 healthy infants (21 singletons and 7 twins) were delivered without major congenital birth defects or malformations. This study showed that AOA with the calcium ionophore ionomycin can improve the reproductive outcomes of patients with previous fertilization failure and poor embryo development after ICSI.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population–based case-control study of women meeting the folic acid recommendations

BackgroundNeural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. ObjectivesTo investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. MethodsData were from the National Birth Defects Prevention Study (United States population–based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 μg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. ResultsNTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. ConclusionsOur findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Extrauterine Growth Retardation—Incidence, Risk Factors, and Prediction Model in Tertiary Care Neonatal Intensive Care Unit in North India

Background With the increasing survival of preterm infants, their nutrition becomes an enormous challenge. Adequate nutrition plays an important role in good neurodevelopmental outcomes. Extrauterine growth retardation (EUGR) is defined as discharge weight below 10th percentile of the weight expected for that gestation after plotting on postnatal growth charts. Aims and Objective This study was conducted to assess the incidence of EUGR in preterm babies and its associated risk factors. Material and Methods This was a retrospective medical chart review of neonates admitted from January 2017 to November 2021 to a level III Neonatal Intensive Care Unit in Delhi, India. Eligible neonates were all preterm babies born at &lt;35 completed weeks’ gestation admitted in NICU within 24 hours of birth and survived for at least 7 days. Neonates who died during hospitalization or were born with a major congenital anomaly requiring surgery in immediate neonatal period or with any genetic syndrome were excluded. Results A total of 250 babies were enrolled in the study, out of which 45.2% neonates were EUGR. Factors significantly associated with EUGR status were long duration of hospital stay, lower birth weight, small for gestational age (SGA) at birth, male sex, persistent ductus arteriosus, sepsis, broncho-pulmonary dysplasia, use of total parenteral nutrition, long duration of mechanical ventilation, longer time to reach full feeds, and interruption of feeds. SGA was associated with highest odds of developing EUGR [OR-80.45 (16.96-1441.09), P&lt;0.001 followed by use of TPN [OR-2.86 (1.61-5.08), p&lt;0.001]. Risk of EUGR increased manifold as the number of risk factors increased. Future plans Strategies for prevention of EUGR should focus on prevention of various neonatal morbidities and risk factor reduction during the hospital stay.

The Effect of Resolution Level and Targeted Design in the Diagnostic Performance of Prenatal Chromosomal Microarray Analysis

Introduction: This study was performed to assess the optimal resolution for prenatal testing by array comparative genomic hybridization (aCGH), aiming to balance between maximum diagnostic yield and minimal detection of variants of uncertain significance (VOUS). Methods: This was a prospective study using data of 2,336 fetuses that underwent invasive prenatal diagnosis, and the samples were analyzed by aCGH. In total, six different aCGH platforms were studied; four different resolutions (0.18 Mb, 0.5 Mb, 1 Mb, and 2 Mb) and two platform designs (whole-genome [WG] and targeted). The results of these designs were compared based on their diagnostic yield and VOUS rate. The performance of the different designs was further analyzed according to indication for invasive testing. Results: The diagnostic yield of copy number variants increased with increasing level of analysis. The detection rates of clinically significant chromosomal abnormalities were almost the same across our targeted array designs; 7.2% with 0.18 Mb backbone/0.05 Mb versus 7.1% with 0.5 Mb backbone/0.05 Mb (p >0.05). However, a significant difference in the rate of VOUS was observed; 9.4% with 0.18 Mb backbone/0.05 Mb versus 6% with 0.5 Mb backbone/0.05 Mb (p <0.001). After analyzing the results across different indications for testing, we found that the application of non-targeted platform designs and lower levels of resolution analysis (such as 1 Mb WG or 0.5 MbL/1 MbG WG) would offer similar diagnostic yield in most cases with major congenital anomalies, with lower VOUS rates. However, the sample size for many indication groups was too small to extract robust associations. Conclusion: It appears that the targeted array platform with 0.5 Mb backbone resolution and 0.05 Mb on targeted gene-rich regions is optimal for routine chromosomal microarray analysis use in prenatal diagnosis. It may be beneficial to individualize the minimum resolution in specific referral indications as the indications for invasive prenatal testing may be quite heterogeneous.

Maternal physical activity, sitting, and risk of non-cardiac birth defects.

The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect. We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects. Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect. Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms. Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations.

Contribution of Preterm Birth to Mortality Among Neonates With Birth Defects

ABSTRACT Birth defects are an important cause of death among infants who die within their first year. Among other complications associated with birth defects, mothers are at higher risk for preterm delivery, which is also associated with infant mortality. Some previous research has shown that in a population of infants with birth defects, those born at term are 3 to 4 times more likely to survive as their preterm peers. This study aimed to clarify the relationship between birth defects, infant mortality, and preterm birth using the population attributable fraction (PAF), examining the mortality risk attributable to preterm birth in infants with birth defects. Data for this study came from the Texas Birth Defects Registry, which includes live births, still births, and pregnancy terminations with a structural birth defect or chromosomal abnormality. The sample included live-born infants with 1 or more major birth defects between January 1, 1999 and December 31, 2014. Exclusion criteria were infants with a chromosomal abnormality or diagnosed syndrome, infants missing data on gestational age or with a gestational age less than 24 weeks, and anencephaly. The final sample included 169,148 infants; of these, 40,872 were preterm (&lt;37 weeks), 128,276 were term, and 2715 died as neonates. Distributions of maternal and infant characteristics were significantly different between the 2 groups (P &lt; 0.01), with more mothers of preterm infants experiencing diabetes, hypertension, multiple gestation pregnancies, or cesarean delivery. In addition, more preterm infants had multiple birth defects or congenital heart defects than their term peers. Analysis of the data included estimates of PAF for infant mortality risk attributed to 31 different birth defects, with results ranging from 12.5% to 71.9%. Highest PAF estimates were observed for anotia or microtia (71.9%; CI, 41.1–86.6), hypospadias (69.4%; CI, 53.9–79.7), talipes equinovarus (69.4%; CI, 60.0–76.6), and stenosis or atresia of the large intestine, rectum, or anal canal (69.1%; CI, 56.3–78.1). On the other hand, lowest PAF estimates included hypoplastic left heart syndrome (12.5%; CI, 8.7–16.1), coarctation of the aorta (19.7%; CI, 9.8–28.4), diaphragmatic hernia (23.8%; CI, 19.2–28.2), and holoprosencephaly (26.0%; CI, 14.5–35.9). For each defect associated with a higher PAF, a large percentage of infant deaths were those born preterm. Infants with defects that had a high PAF estimate were 11.4–17.8 times more likely to die if born preterm than term, and those with a low PAF estimate were only 1.9–2.3 times more likely to die if born preterm as opposed to full term. Overall, analysis showed that 51.7% of neonatal mortality in infants with birth defects is attributable to preterm birth. Stratified analyses performed to reduce confounders showed similar results. The relationship between birth defects and other factors contributing to preterm delivery and infant mortality is complex, and thus this study is unable to fully characterize these relationships. The associations revealed in this analysis indicate that preterm birth is a significant contributor to infant mortality in infants with birth defects, and further research can more fully characterize this association by attempting interventions both to mitigate preterm birth and to reduce infant mortality after preterm birth. Further research might also focus on particular types of birth defects and how rates of preterm birth might be reduced in specific cases of either infant or maternal risks.

Umbilical Cord Milking in Nonvigorous Infants: A Cluster-Randomized Crossover Trial

ABSTRACT Approximately 6 million infants each year require resuscitation at birth. Requiring this intervention is associated with higher risk of hypoxic-ischemic encephalopathy (HIE), cerebral palsy, attention-deficit or hyperactive disorder, autism, neonatal stroke, and death. In infants needing resuscitation, optimal cord management is essential to enhance placental transfusion. Delayed cord clamping (DCC) is used to enable placental transfusion in vigorous infants, but in nonvigorous infants—those who are limp, pale, or have minimal or no breathing—early cord clamping (ECC) is recommended. Another intervention for nonvigorous infants requiring resuscitation is umbilical cord milking (UCM). UCM can improve heart rate, blood pressure, urine output, cerebral oxygenation, and hemoglobin levels, and prevent anemia. In addition, it can achieve placental transfusion without delaying resuscitation as with DCC and can be completed as quickly as ECC. No harm has been observed in studies involving UCM. Despite these benefits, studies are lacking on optimal cord management strategies in nonvigorous infants requiring resuscitation. The aim of this study was to examine whether UCM reduces admission to the neonatal intensive care unit (NICU) versus ECC in nonvigorous newborns. This was a pragmatic, cluster-randomized, crossover trial conducted at 10 hospitals in the United States, Canada, and Poland. Included were viable infants delivered between January 2019 and May 2021 who were between 35 and 42 weeks of gestation and nonvigorous at birth. Nonvigorous was defined as poor tone, pallor, or lack of breathing in the first 15 seconds after birth. Excluded were infants with major congenital or chromosomal anomalies, cardiac defects except small ventricular septal defects, complete placental abruption or cutting through the placenta at delivery, monochorionic multiples, cord anomalies, and the presence of nonreducible nuchal cord. Hospitals were randomized 1:1 to UCM or ECC in period 1 from January 2019 to January 2020, then crossed over to the other intervention during period 2 from February 2020 to May 2021. The primary outcome was NICU admission related to the intervention in the first 24 hours of life. The safety outcome was HIE. A total of 1730 infants were included in the analysis with 872 in the UCM group and 858 in the ECC group. The difference in the frequency of NICU admission was not statistically significant, with 23% in the UCM group and 28% in the ECC group (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.41–1.14). In comparison to the ECC group, UCM was associated with lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%; crude OR, 0.72; 95% CI, 0.56–0.92), receipt of cardiorespiratory support in the delivery room (61% vs 71%; modeled OR, 0.57; 95% CI, 0.33–0.99), and therapeutic hypothermia (3% vs 4%; crude OR, 0.58; 95% CI, 0.33–0.99). In addition, there was no significant difference in any grade of HIE, although moderate-to-severe HIE was less common in the UCM group (1% vs 3%; crude OR, 0.48; 95% CI, 0.24–0.96). The UCM group also had increased hemoglobin (modeled mean difference, 0.68 g/dL; 95% CI, 0.31–1.05) and peak serum bilirubin (modeled mean difference, 1.4 mg/dL; 95% CI, 0.5–2.2). In nonvigorous newborns needing resuscitation, UCM was not associated with a reduction in NICU admissions compared with ECC. UCM was associated with a decrease in cardiorespiratory support in the delivery room, fewer cases of moderate-to-severe HIE, lower use of therapeutic hypothermia, and higher hemoglobin.

Neonatal morbidity and mortality patterns in NICU at Al-Ameen Medical College and Hospital, Bijapur

Background: Despite improvements in perinatal care, there is still a high rate of neonatal morbidity and mortality in developing nations like India. Neonatal period is defined as from birth upto first 28 days of life. Methods: An observational prospective study was done with sample size of 600 babies admitted in NICU at AMCH, Bijapur during the period from January 2021 to August 2022. During the 18 months period of study, data was collected based on babies admitted with respect to gestational age, weight and day of life. Results: The data analysis for morbidity showed that respiratory distress syndrome 24.6%, birth asphyxia with HIE 18.7%, jaundice 17.5%, sepsis 12.3%, meconium aspiration syndrome 4.7%, major congenital anomaly 3.4%, respiratory distress (other causes) 1.8%, others 17.3%. The disease wise mortality among neonates admitted to nicu was studied and were found that respiratory distress syndrome 35.5%, birth asphyxia with HIE 25.4%, sepsis 23.3%, major congenital malformations 6.1%, meconium aspiration syndrome 5.5%, others 4.1%. Conclusions: The most common causes of admission were respiratory distress syndrome, birth asphyxia, jaundice, sepsis, meconium aspiration syndrome and major congenital anomalies. The most common causes of mortality were respiratory distress syndrome, birth asphyxia, sepsis and major congenital malformations.

Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine: a retrospective real-world study in China

ABSTRACTBackgroundThe 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure.Research design and methodsWomen who received the first dose of the 9vHPV vaccine at age 16–26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected.ResultsA total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto’s, 11 Graves’, and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed.ConclusionsIn this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.