Sudhir Sriram

Relationship of cesarean delivery to lower birth weight-specific neonatal mortality in singleton breech infants in the United States.

OBJECTIVE The preferred route of delivery for breech presentation has been controversial. We compared the birth weight-specific neonatal mortality of vaginal births to cesarean births in singleton births with breech presentation. METHODS A total of 371,692 singleton live births with breech presentation were selected for the study from the United States birth cohorts for the years 1989-1991. Differences in birth weight specific mortality were compared using a z-statistic for differences in proportions and by logistic regression. RESULTS Compared to primary vaginal births, primary cesarean births had significantly lower neonatal mortality for all birth weight groups, despite increased prevalence of fetal malformations in the cesarean as compared with vaginally delivered group. This mortality difference was greatest in the first hour of life. Difference in overall neonatal (less than 28 days) mortality rate ranged from a low of 1.6-fold in the 500-749 g group (726.6 per 1000 vaginal births compared with 456.3 per 1000 cesarean births, P < .001) to as high as about three-fold in the 1250-1499 g group (232.9 per 1000 vaginal births compared to 72.5 per 1000 cesarean births, P < .001). In the group with birth weights over 2500 g, neonatal mortality in the primary vaginal births was 5.3 per 1000 and in the primary cesarean births, 3.2 per 1000 (P < .001). Similarly, repeat cesarean births had significantly lower birth weight-specific neonatal mortality, compared with vaginal births after previous cesarean. CONCLUSION Singleton live births with breech presentation delivered by cesarean had lower birth weight-specific neonatal mortality as compared with vaginal births.

A survey of the newborn populations in Belgium, Germany, Poland, Czech Republic, Hungary, Bulgaria, Spain, Turkey, and Japan for the G985 variant allele with haplotype analysis at the medium chain Acyl-CoA dehydrogenase gene locus: Clinical and evolutionary consideration

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of fatty acid metabolism. It is one of the most frequent genetic metabolic disorders among Caucasian children. The G985 allele represented 90% of all the variant alleles of the MCAD gene in an extensive series of retrospective studies. To study the distribution of the G985 allele, newborn blood samples from the following countries were tested; 3000 from Germany (1/116). 1000 each from Belgium (1/77). Poland (1/98), Czech Republic (1/240). Hungary (1/168), Bulgaria (1/91), Spain (1/141). Turkey (1/216), and 500 from Japan (none). The frequency is shown in parentheses. The haplotype of G985 alleles in 1 homozygote and 57 heterozygote samples were then analyzed using two intragenic MCAD gene polymorphisms (Iaq1 and GT-repeat). The result indicated that only 1 of the 10 known haplotypes was associated with the G985 mutation, suggesting that G985 was derived originally from a single ancestral source. We made a compilation of the G985 frequencies in these countries and those in nine other European countries studied previously. The G985 distribution was high in the area stretching from Russia to Bulgaria in the east and in all northern countries in western and middle Europe, but low in the southern part of western and middle Europe. The incidence among ethnic Basques appeared to be low. This distribution pattern and the fact that all G985 alleles belong to a single haplotype suggest that G985 mutation occurred later than the delta F508 mutation of the CFTR, possibly in the neolithic or in a later period, and was brought into Europe by IndoEuropean-speaking people. The panEuropean distribution of the G985 allele, including Slavic countries from which patients with MCAD deficiency have rarely been detected, indicates the importance of raising the level of awareness of this disease.

Acute hemodynamic effects of caffeine administration in premature infants

Objective:Administration of caffeine citrate (caffeine) has been a central component of the treatment of apnea of prematurity. However, given its multiple pharmacologic effects, caffeine might be expected to produce hemodynamic changes in heart rate, stroke volume, cardiac output and vascular resistance.Study Design:In this prospective observational study, we report the hemodynamic effects of intravenous caffeine administration in a population of premature infants who received caffeine to correct or prevent apnea of prematurity.Methods:Hemodynamic effects of caffeine were determined in 31 infants. Stroke volume was measured via echocardiogram, using velocity time integral at the aortic root diameter. Statistically univariate analyses were performed parametrically using paired t-test and nonparametrically (sign test). Multivariate linear regression models were used to identify subgroup covariate effects.Results:After intravenous caffeine, cardiac index increased in 31 of 31 trials, by an average of 14.6±16.3% (s.d.); stroke volume increased in 24 of 31 trials, by 7.8±12.2%; heart rate increased in 28 of 31 trials by 7.7±7.2 beats per min; and blood pressure increased in 25 of 31 trials, by 4.1±5.8 mm Hg (all P<0.001). Multivariate linear regression revealed no significant effect of dose, birth weight, gestational age or postnatal age.Conclusions:Intravenous caffeine consistently increases cardiac output and blood pressure in relatively stable premature infants, when given to treat or prevent apnea of prematurity. We speculate that there may be a role for caffeine in the hemodynamic treatment of hypotensive/hypoperfused infants.

Extracorporeal membrane oxygenation and term neonatal respiratory failure deaths in the United Kingdom compared with the United States: 1999 to 2005.

Objective: To compare national neonatal extracorporeal membrane oxygenation data and deaths from primary respiratory disorders of term neonates between the United Kingdom and the United States from 1999 to 2005. Design: Cross-sectional study. Setting: National data sets from the United Kingdom and the United States. Patients: Neonatal extracorporeal membrane oxygenation patients submitted to the Extracorporeal Life Support Organization Registry and national birth and death registrations. Interventions: None. Measurements and Main Results: Meconium aspiration syndrome was the most common indication for extracorporeal membrane oxygenation in the United Kingdom: 50.6% vs. 25.8% in the United States (p < .001). Congenital diaphragmatic hernia was most common indication for extracorporeal membrane oxygenation in the United States: 30.7% vs. 15.4% in the United Kingdom (p < .001). Extracorporeal membrane oxygenation use was greater in the United States than the United Kingdom: rate ratio, 1.81 (95%, confidence interval, 1.64, 2.00). The extracorporeal membrane oxygenation rate decreased over time in the United States (p < .001) but was unchanged for all diagnoses in the United Kingdom (p = .49). The rates of extracorporeal membrane oxygenation use for meconium aspiration syndrome were equivalent in both countries: rate ratio, 0.92 (95% confidence interval, 0.80, 1.07) but greater in the United States for congenital diaphragmatic hernia: rate ratio, 3.60, (95% confidence interval, 2.82, 4.66) and persistent pulmonary hypertension newborn: rate ratio, 4.67 (95% confidence interval, 3.33, 6.74). National neonatal death rates included nonextracorporeal membrane oxygenation + extracorporeal membrane oxygenation death. Meconium aspiration syndrome deaths were equivalent overall between the two countries: rate ratio, 0.99 (95% confidence interval, 0.77, 1.29), but decreased in the United States (p < .001) although not in the United Kingdom (p = .17). Congenital diaphragmatic hernia deaths were more prevalent in the United Kingdom than in the United States: rate ratio, 1.57 (95% confidence interval, 1.34, 1.84). Conclusions: Extracorporeal membrane oxygenation is used more often in the United States: clinicians seem less willing to offer extracorporeal membrane oxygenation for persistent pulmonary hypertension of the newborn and congenital diaphragmatic hernia in the United Kingdom. In contrast to the United States, no reduction in either extracorporeal membrane oxygenation use or death due to meconium aspiration syndrome was observed in the United Kingdom. Early transfer to a tertiary center is recommended for term neonates with respiratory failure.

Birth Outcomes of Koreans by Birthplace of Infants and Their Mothers, the United States versus Korea, 1995-2004

The acculturation effect of immigrant women on birth outcomes varies by race. We examined birth outcomes of three groups of births for the period 1995-2004, USA births to the USA-born Korean mothers, USA births to the non-USA-born Korean mothers, and births in Korea. In singleton USA births to both Korean parents, average birth weight was 3,294 g for the USA-born Korean mothers and 3,323 g for the non-USA-born Korean mothers. However, this difference was not significant, once controlled for other maternal sociodemographic, obstetric and medical factors. Low birth weight and prematurity prevalence were not different by maternal nativity between these two singleton groups. Average birth weight of all births including multiplets in Korea was 3,270 g, compared to 3,297 g for all USA-born infants including multiplets and births either to both or one Korean parents. This difference might have reflected a significantly lower educational attainment of mothers in Korea compared to Korean mothers in the USA. Low birth weight rate was consistently lower in infants born in Korea compared to the USA-born, but this difference became less, 4.2% and 4.6% respectively by 2004. These observations suggest that in the USA acculturation effect of Korean immigrants on birth outcomes is negligible.

Neonatal and Infant Mortality in Korea, Japan, and the U.S.: Effect of Birth Weight Distribution and Birth Weight-Specific Mortality Rates.

Difference in crude neonatal and infant mortality rates (NMR and IMR) among different countries is due to the differences in its two determinants: birth weight distribution (BWD) and birth weight-specific mortality rates (BW-SMRs). We aimed to determine impact of BWD and BW-SMRs on differences in crude NMR and IMR among Korea, Japan, and the U.S. Our study used the live birth data of the period 2009 through 2010. Crude NMR/IMR are the lowest in Japan, 1.1/2.1, compared to 1.8/3.2, in Korea, and 4.1/6.2, in the U.S., respectively. Japanese had the best BW-SMRs of all birth weight groups compared to the Koreans and the U.S. The U.S. BWD was unfavorable with very low birth weight (< 1,500 g) rate of 1.4%, compared to 0.6% in Korea, and 0.8% in Japan. If Koreans and Japanese had the same BWD as in the U.S., their crude NMR/IMR would be 3.9/6.1 for the Koreans and 1.5/2.5 for the Japanese. If both Koreans and Japanese had the same BW-SMRs as in the U.S., the crude NMR/IMR would be 2.0/3.8 for the Koreans and 2.7/5.0 for the Japanese. In conclusion, compared to the U.S., lower crude NMR or IMR in Japan is mainly attributable to its better BW-SMRs. Koreans had lower crude NMR and IMR, primarily from its favorable BWD. Comparing crude NMR or IMR among different countries should include further exploration of its two determinants, BW-SMRs reflecting medical care, and BWD reflecting socio-demographic conditions.

Early Blood Gas Predictors of Bronchopulmonary Dysplasia in Extremely Low Gestational Age Newborns

Aim. To determine among infants born before the 28th week of gestation to what extent blood gas abnormalities during the first three postnatal days provide information about the risk of bronchopulmonary dysplasia (BPD). Methods. We studied the association of extreme quartiles of blood gas measurements (hypoxemia, hyperoxemia, hypocapnea, and hypercapnea) in the first three postnatal days, with bronchopulmonary dysplasia, among 906 newborns, using multivariable models adjusting for potential confounders. We approximated NIH criteria by classifying severity of BPD on the basis of the receipt of any O2 on postnatal day 28 and at 36 weeks PMA and assisted ventilation. Results. In models that did not adjust for ventilation, hypoxemia was associated with increased risk of severe BPD and very severe BPD, while infants who had hypercapnea were at increased risk of very severe BPD only. In contrast, infants who had hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated the associations with hypoxemia and with hypercapnea and made the decreased risk of very severe BPD statistically significant. Conclusions. Among ELGANs, recurrent/persistent blood gas abnormalities in the first three postnatal days convey information about the risk of severe and very severe BPD.

Cognitive Development and Quality of Life Associated With BPD in 10-Year-Olds Born Preterm

Children born premature and experiencing BPD are at increased risk for neurocognitive, behavioral, and social dysfunctions. OBJECTIVES: To compare neurocognitive, language, executive function, academic achievement, neurologic and behavioral outcomes, and quality of life at age 10 years in children born extremely preterm who developed bronchopulmonary dysplasia (BPD) to children who did not develop BPD. METHODS: The Extremely Low Gestational Age Newborns study population included 863 children born extremely preterm whose BPD status before discharge was known had an IQ (Differential Ability Scales II [DAS II]) assessment at 10 years. We evaluated the association of BPD with any cognitive (DAS II), executive function (NEuroPSYchological Assessment II), academic achievement (Wechsler Individual Achievement Test-III and Oral and Written Language Scales [OWLS]) as well as social dysfunctions (Social Responsiveness Scale). We used logistic regression models, adjusting for potential confounding factors, to assess the strength of association between the severity of BPD and each outcomes. RESULTS: Three hundred and seventy-two (43%) children were oxygen-dependent at 36 weeks postconception age, whereas an additional 78 (9%) were also oxygen- and ventilator-dependent. IQ scores 2 or more SDs below the expected mean (ie, z scores ≤−2) occurred twice as commonly among children who had BPD as among those who did not. Children with severe BPD consistently had the lowest scores on DAS II, OWLS, Wechsler Individual Achievement Test-III, NEuroPSYchological Assessment II, and Social Responsiveness Scale assessments. CONCLUSIONS: Among 10-year-old children born extremely preterm, those who had BPD were at increased risk of cognitive, language, and executive dysfunctions; academic achievement limitations; social skill deficits; and low scores on assessments of health-related quality of life.

Manifestations of Cow's-milk Protein Intolerance in Preterm Infants

Objectives: Cows-milk protein intolerance (CMPI) is poorly recognized in preterm infants. This study examined the clinical events that preceded the diagnosis of CMPI in preterm infants. Methods: This was a retrospective study of infants in a level-III neonatal intensive care unit of those who received parenteral nutrition (PN) support during a 12-month period. Parameters assessed included birth weight (g), diagnosis, duration and frequency on PN, type of enteral feeds at initiation, and achievement of enteral autonomy. CMPI was diagnosed based on persistent feeding intolerance that resolved after change of feeds from intact protein to a protein hydrolysate or crystalline amino acid formula. Results: Three hundred forty-eight infants with birth weight (median/range) 1618 g (425–5110) received PN. Fifty-one (14%) infants required multiple courses of PN, and 19 of 348 (5%) were diagnosed with CMPI. The requirement for multiple courses on PN versus single course was associated with a high likelihood of CMPI: 14 of 51 versus 5 of 297, P < 0.001. Nine of the 14 infants identified with CMPI were initially diagnosed with necrotizing enterocolitis (NEC) after a median duration of 22 days (19–57) on intact protein feeds. After recovery from NEC, they had persistent feeding intolerance including recurrence of “NEC-like illness” (N = 3) that resolved after change of feeds to a protein hydrolysate or crystalline amino acid formula. Conclusions: The requirement for multiple courses of PN because of persistent feeding intolerance after recovery from NEC and recurrence of “NEC-like illness” may be a manifestation of CMPI in preterm infants.

Births to Parents with Asian Origins in the United States, 1992–2012

Despite a remarkable increase in Asian births in the U.S., studies on their birth outcomes have been lacking. We investigated outcomes of births to Asian parents and biracial Asian/White parents in the U.S. From the U.S. birth data (1992–2012), we selected singleton births to Korean, Chinese, Japanese, Filipino, Asian Indian, and Vietnamese. These births were divided into three groups; births to White mother/Asian father, Asian mother/White father, and births to the both ethnic Asian parents. We compared birth outcomes of these 18 subgroups to those of the White mother/White father group. Mean birthweights of births to the Asian parents were significantly lower, ranging 18 g to 295 g less than to the White parents. Compared to the rates of low birthweight (LBW) (4.6%) and preterm birth (PTB) (8.5%) in births to the White parents, births to Filipino parents had the highest rates of LBW (8.0%) and PTB (11.3%), respectively, and births to Korean parents had the lowest rates of both LBW (3.7%) and PTB (5.5%). This pattern of outcomes had changed little with adjustments of maternal sociodemographic and health factors. This observation was similarly noted also in births to the biracial parents, but the impact of paternal or maternal race on birth outcome was different by race/ethnicity. Compared to births to White parents, birth outcomes from the Asian parents or biracial Asian/White parents differed depending on the ethnic origin of Asian parents. The race/ethnicity was the strongest factor for this difference while other parental characteristics hardly explained this difference.