Hyperbilirubinemia and neurodevelopmental outcome of very low birthweight infants: results from the LIFT cohort

Background

Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent.

Objective

To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants.

Methods

Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels'' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL.

Results and Conclusions

A total of 724 infants were included in the study, and among them, 631 (87%) were evaluated at two years old. The infants of the first tertile were younger and smaller than the infants of the other two tertiles, in accordance with Maisels'' recommendations for very small infants. No difference in the risk of impaired functional outcome among the three groups was observed. However, among infants weighing less than 1001 g, those in the third tertile had a poorer neurodevelopmental prognosis as compared to those in the second tertile (adjusted odds ratio = 6.8, 95% CI: 1.2–36.7, p = 0.03). Considering the results obtained, we propose 196 µmol/L (11.5 mg/dL) when birthweight varies between 1001 and 1500 g, and 170 µmol/L (9.9 mg/dL) when birthweight is less than 1001 g, as recommended max-SBLs (defined as maximal levels of 95^th percentile curves of SBLs in infants with an optimal outcome). When Maisels'' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001–1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels'' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g.     

Genetic and non-genetic factors affecting birth-weight and adult Body Mass Index.

Birthweight affects neonatal mortality and morbidity and has been used as a marker of foetal undernutrition in studies of prenatal effects on adult characteristics. It is potentially influenced by genetic and environmental influences on the mother, and effects of foetal genotype, which is partially derived from the maternal genotype. Interpretations of variation in birthweight and associated characteristics as being due to prenatal environment ignore other possible modes of materno-foetal transmission. Subjects were adult twins recruited through the Australian Twin Registry, aged 17 to 87 years, and the sample comprised 1820 men and 4048 women. Twins reported their own birthweight as part of a health questionnaire. Body Mass Index (BMI) was calculated from self-reports of height and weight. Correlations between co-twins' birthweights were high for both monozygotic (r = 0.77) and dizygotic (r = 0.67) pairs, leading to substantial estimates of shared environmental effects (56% of variance) with significant additive genetic (23%) and non-shared environmental (21%) components. Adult BMI was mainly influenced by genetic factors, both additive (36% of variance) and nonadditive (35%). The correlation between birthweight and BMI was positive, in that heavier babies became on average more obese adults. A bivariate model of birthweight and adult BMI showed significant positive genetic (r(g) = 0.16, p = 0.005) and environmental (r(e) = 0.08, p = 0.000011) correlations. Intra-uterine environmental or perinatal influences shared by cotwins exercise a strong influence on birthweight, but the factors which affect both birthweight and adult BMI are partly genetic and partly non-shared environmental.     

Outcome of pregnancy in underweight women after spontaneous and induced ovulation

Low maternal weight before pregnancy and poor weight gain during pregnancy are known to result in an increased prevalence of low birthweight infants. Low body weight is also an important cause of amenorrhoea. The hypothesis that amenorrhoeic underweight women who become pregnant after induction of ovulation are more at risk of delivering low birthweight infants than underweight women who ovulate spontaneously was investigated. Forty one pregnant women in whom ovulation had been induced and 1212 in whom ovulation was spontaneous were studied. Women ovulating spontaneously whose weight was normal and who showed good weight gain during pregnancy (>450 g a week) had the lowest incidence (6%) of babies who were small for gestational age. Underweight women (body mass index <19·1) who ovulated spontaneously had a threefold increased risk of delivering babies who were small for gestational age (18%). Overall, the women in whom ovulation had been induced had an even higher risk of babies who were small for dates (25%), and this risk was greatest (54%) in those who were underweight.The outcome of pregnancy is related to weight before conception, which in many cases reflects nutritional state; lack of spontaneous ovulation indicates an increased risk of producing a small for dates infant. The most suitable treatment for infertility secondary to weight related amenorrhoea is therefore dietary rather than induction of ovulation.     

Effectiveness of neonatal transport.

The condition of 259 infants transferred to the neonatal intensive care unit (NICU) of the Montreal Children''s Hospital from Oct. 1, 1974 to Mar. 31, 1975 was evaluated. Their transport was provided by personnel and equipment from the Montreal Children''s Hospital. When the transport team arrived at the referring hospital hypothermia (temperature of less than 36 degrees C) was present in 25.2% of the 163 infants for whom complete temperature measurements were available. Most (77.3%) of the infants were warmed during transport and only 3.1% arrived at the NICU with a temperature of less than 35 degrees C. The mortality was significantly higher in babies of all birth weight groups whose core temperature had been below the optimal temperature for survival (36 to 37 degrees C). It appears that the use of appropriate equipment and trained personnel can reduce the incidence of hypothermia and therefore the mortality in infants requiring transfer.     

Birth Outcomes of Latin Americans in Two Countries with Contrasting Immigration Admission Policies: Canada and Spain

Background

We delved into the selective migration hypothesis on health by comparing birth outcomes of Latin American immigrants giving birth in two receiving countries with dissimilar immigration admission policies: Canada and Spain. We hypothesized that a stronger immigrant selection in Canada will reflect more favourable outcomes among Latin Americans giving birth in Canada than among their counterparts giving birth in Spain.

Materials and Methods

We conducted a cross-sectional bi-national comparative study. We analyzed birth data of singleton infants born in Canada (2000–2005) (N = 31,767) and Spain (1998–2007) (N = 150,405) to mothers born in Spanish-speaking Latin American countries. We compared mean birthweight at 37–41 weeks gestation, and low birthweight and preterm birth rates between Latin American immigrants to Canada vs. Spain. Regression analysis for aggregate data was used to obtain Odds Ratios and Mean birthweight differences adjusted for infant sex, maternal age, parity, marital status, and father born in same source country.

Results

Latin American women in Canada had heavier newborns than their same-country counterparts giving birth in Spain, overall [adjusted mean birthweight difference: 101 grams; 95% confidence interval (CI): 98, 104], and within each maternal country of origin. Latin American women in Canada had fewer low birthweight and preterm infants than those giving birth in Spain [adjusted Odds Ratio: 0.88; 95% CI: 0.82, 0.94 for low birthweight, and 0.88; 95% CI: 0.84, 0.93 for preterm birth, respectively].

Conclusion

Latin American immigrant women had better birth outcomes in Canada than in Spain, suggesting a more selective migration in Canada than in Spain.     

Glucose polymer supplementation of feeds for very low birthweight infants.

The feeds of 14 very low birthweight infants (birth weight less than 1500 g) were supplemented with a glucose polymer (Caloreen) at the rate of 6 g/kg body weight daily. Seven day periods of supplementation were alternated with seven day periods of normal feeding. Adding the glucose polymer significantly increased the rate of weight gain in these infants from 105 g/week to 140 g/week; growth rates in terms of length and head circumference were not affected. No adverse effects were noted. Glucose polymer is a useful energy supplement for very low birthweight infants.     

The influence of a male twin on birthweight of its female co-twin - a population-based study.

Fetal growth is influenced by various determinants, with males being heavier than females. It was recently suggested that female birthweight tends to be increased by the presence of a male co-twin. We evaluated this hypothesis in the Israeli population. We reviewed a retrospective population database of the 1993-1998 Israeli Birth Registry. We compared male birthweight in the male-male and male-female combination sets and female birthweight in the female-female and male-female combination sets. We compared the mean birthweight of males and females in three groups of total twin birthweight. The sample of 12,686 sets included 50.6% males. The male-male combination was found in 31.3% sets, female-female in 38.7% and unlike-sex combination in 30.0%. A total twin birthweight of less than 3000g was found in 7.2% sets, of 3001-5000g in 50.7% sets, and of over 5000g in 42.1% sets. The mean male birthweight was 2398 +/- 602 g and the mean female birthweight was 2316 +/- 566g, p <.0001 (95% CI of 67, 96). The mean birthweight of males in the male-male combination was significantly lower than in the unlike-sex combination, p <.0001, in total birthweights over 3000g. No significant difference was found between the mean birthweight of females in the female-female and in the unlike-sex combinations in all total birthweight strata. Our findings do not substantiate a male-related inter-twin influence on female birthweight. Population differences might underlie the opposing observations in the literature.     

Long-term implications of feed energy source in different genetic types of reproductive rabbit females: III. Fitness and productivity

The specialization process associated with genetic selection could be associated with functional disorders, affecting the reproductive success of females (fitness). We hypothesized that by modulating energy acquisition and allocation of females we could balance productivity and reproductive success. To test this hypothesis, we used 203 rabbit females belonging to three genetic types: H (n=66) maternal line specialized in prolificacy, LP (n=67) generalist maternal line, R (n=70) paternal line specialized in growth rate. We fed each genetic type with two diets specifically designed to promote milk yield (AF) or body reserves recovery (CS). We controlled females between their first and fifth reproductive cycles, recording traits related with productivity and fitness of females. H females fed CS had on average 11.2±0.43 kits with an individual weight of 54±1.2 g at birth and 525±11 g at weaning. Their conception rate when multiparous was 44% and their survival rate at the end of the experiment 30%. When they were fed AF, the individual weight of kits was 3.8 g heavier (P<0.05) at birth and 38 g heavier at weaning (P<0.05), the conception rate when multiparous increased 23 percentage points (P<0.05) and the survival rate at the end of the experiment 25 percentage points (P<0.05). LP females fed CS had on average 10.8±0.43 kits with an individual weight of 52±1.2 g at birth and 578±11 g at weaning. Their conception rate when multiparous was 79% and their survival rate at the end of the experiment 75%. When they were fed AF, it only increased individual weight of kits at weaning (+39 g; P<0.05). R females fed CS had on average 8.4±0.43 kits with an individual weight of 60±1.2 g at birth and 568±11 g at weaning. Their conception rate when multiparous was 60% and their survival rate at the end of the experiment 37%. When they were fed AF, they presented 1.4 kits less at birth (P<0.05) but heavier at birth (+4.9 g; P<0.05) and at weaning (+37 g; P<0.05). Therefore, we observed that genetic types prioritized different fitness components and that diets could affected them. In this sense, seems that more specialized genetic types, were more sensitive to diets than the more generalist type.     

A partial explanation of superior birth weights among foreign-born women

This study of 766 black women reexamined the issue of advantage in birthweight and length of gestation in foreign-born women and confirms the reported higher birthweights among that group. Subjects were new registrants for prenatal care at a public clinic in Harlem, New York City, 1971-73, and were part of a randomized trial of nutritional supplementation during pregnancy. 3 nativity groups were represented: New York City, southern United States, and foreign countries. Despite the standard selection of all subjects for high risk for low birthweight, foreign-born women had only 3.8% of births under 2500 grams in contrast to 15.6% among the southern women, and 18% among New York City natives. 6 sets of variables were examined in relation to birthweight outcome. An average birthweight advantage of 218 grams for the foreign-born was found to be associated with higher childhood social status and more positive health behaviors.     

The relationship between parental age and birth order with the percentage of low birth-weight infants

Birthweight, birth order, and parental age were abstracted from 1,515,443 New York State birth certificates to study the association between the birth of an infant weighing less than 2501 g and parental age. The percentage of premature infants was greatest for birth order 1 and 6+ and showed a minimum at birth order 3. When maternal age and birth order were analyzed jointly, a strong interaction was found. Young mothers showed a tendency to have an increasing proportion of low birthweight infants with increasing birth order, whereas, the exact opposite was true for mothers older than 45. The intermediate maternal age categories reflected this change from an association of increasing proportion of low birthweight infants with increasing birth order to a pattern of decreasing proportion of premature imfants with increasing birth order. In data stratified to eliminate the influence of maternal age and to some extent birth order, paternal age was shown to affect the percentage of infants weighing less than 2501 g. This association was described by a flat n-shaped curve that was significantly different from a horizontal line (P.01) in 6 of 7 maternal age categories.     

Costs and benefits of a community special care baby service

Between January 1981 and December 1986 3829 low birthweight (<2500 g) infants and 1980 other high risk infants were cared for at home after they were discharged from hospital by a specialist neonatal nursing service. Of the infants who were referred to this service, 720 (12%) weighed under 2000 g and 1919 (33%) under 2250 g at the time of discharge home. The infants were visited by the community neonatal sisters on an average of 11 occasions, but the number of visits varied from six to over 100 depending on the needs of the child and parents. There was close liaison with other community and hospital staff. Two hundred and thirty (4%) referred infants were readmitted to hospital while under the care of the specialist nursing service. In 1985 the cost of the service was £127 000, or £123 for each infant referred. Providing this specialist support at home allowed much earlier discharge of low birthweight infants from hospital. When compared with the cost of providing continuing inpatient neonatal care earlier discharge was estimated to have saved roughly £250 000 in 1985.Low birthweight infants have an increased risk of serious illness or death that extends beyond the neonatal period. Many are born to young and socially disadvantaged parents who can benefit from expert guidance and support at home. A community neonatal nursing service has advantages for high risk infants and their parents, is cost effective, and allows more efficient use of limited hospital resources.     

Compliance of a cobalt chromium coronary stent alloy – the COVIS trial

Aim

Female cardiac transplant recipients' aerobic capacity is 60% lower than sex and age-predicted values. The effect of exercise training on restoring the impaired aerobic endurance and muscle strength in female cardiac transplant recipients is not known. This study examined the effect that aerobic and strength training have on improving aerobic endurance and muscle strength in female cardiac transplant recipients.

Methods

20 female cardiac transplant recipients (51 ± 11 years) participated in this investigation. The subjects performed a baseline six-minute walk test and a leg-press strength test when they were discharged following cardiac transplantation. The subjects then participated in a 12-week exercise program consisting of aerobic and lower extremity strength training. Baseline assessments were repeated following completion of the exercise intervention.

Results

At baseline, the cardiac transplant recipients' aerobic endurance was 50% lower than age-matched predicted values. The training program resulted in a significant increase in aerobic endurance (pre-training: 322 ± 104 m vs. post-training: 501 ± 99 m, p < 0.05) and leg-press strength (pre-training: 48 ± 16 kg. vs. post-training: 78 ± 27 kg, p < 0.05).

Conclusion

Aerobic and strength training are effective interventions that can partially restore the impaired aerobic endurance and strength found in female cardiac transplant recipients.     

Relation between early introduction of solid food to infants and their weight and illnesses during the first two years of life.

OBJECTIVE--To assess the relations between early introduction of solid food and infant weight, gastrointestinal illness, and allergic illnesses during the first two years of life. DESIGN--Prospective observational study of infants followed up for 24 months after birth. SETTING--Community setting in Dundee. PATIENTS--671 newborn infants, of whom 455 were still available for study at 2 years of age. MAIN OUTCOME MEASURES--Infants'' diet, weight, and incidence of gastrointestinal illness, respiratory illness, napkin dermatitis, and eczema at 2 weeks and 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24 months of age. RESULTS--The infants given solid food at an early age (at < 8 weeks or 8-12 weeks) were heavier than those introduced to solids later (after 12 weeks) at 4, 8, 13, and 26 weeks of age (p < 0.01) but not at 52 and 104 weeks. At their first solid feed those given solids early were heavier than infants of similar age who had not yet received solids. The incidence of gastrointestinal illness, wheeze, and nappy dermatitis was not related to early introduction of solids. There was a significant but less than twofold increase in respiratory illness at 14-26 weeks of age and persistent cough at 14-26 and 27-39 weeks of age among the infants given solids early. The incidence of eczema was increased in the infants who received solids at 8-12 weeks of age. CONCLUSION--Early introduction of solid food to infants is less harmful than was previously reported. Longer follow up is needed, but, meanwhile, a more relaxed approach to early feeding with solids should be considered.     

Weight variation by sex and nature of risk factors in high-risk infants: an evolutionary perspective

A retrospective cohort study was conducted to explore growth variation during the intrauterine and early postnatal period by sex and nature of high-risk factors (i.e. physiological and pathological) in 831 Korean infants at a University hospital. The results showed that infants with a physiological risk showed a more congruent intrauterine growth pattern compared to those with a pathological risk. Particularly with a physiological risk, female infants experienced more compatible intrauterine and postnatal growth than males, although male infants were heavier than female infants at a given gestational age. In conclusion bigger may not necessarily be better for prenatal growth in humans. A more confluent intrauterine growth in infants with physiological risk can be beneficial for early postnatal catch-up growth. From an evolutionary perspective, female infants with a physiological risk may keep their advantageous edge over male infants during the early postnatal period although such an advantage may not be present with a pathological condition.     

Effect of long-term selection for early postnatal growth rate on survival and prenatal development of transferred mouse embryos

Reciprocal embryo transfer procedures were performed among mouse selection lines to examine prenatal maternal effects on survival and development of transferred embryos. Mice were from generations 28 and 29 of an experiment to select for (i) increased body weight again from 0 to 10 days (E+); (ii) decreased body weight gain from 0 to 10 days (E-); or (iii) a randomly bred control line (C). A total of 118 embryo transfer procedures performed 12 h after conception resulted in 983 progeny born to 89 litters. There was a 39% overall embryo survival rate and 75% overall pregnancy success rate. Response to superovulation and oestrous synchronization was significantly lower (P < 0.01) in the E+ line. E+ individuals that did superovulate produced an average of 37 oocytes per flush, which was significantly higher than in the control line mice (29 oocytes per flush; P < 0.01). The ability to complete pregnancy successfully was not influenced by uterine environment or embryo-uterine interaction. In contrast, embryo survival in successful pregnancies was significantly affected by uterine environment. There were large maternal effects for body weight and tail length at birth; E+ recipients produced pups that were significantly larger than E- recipient pups (P < 0.01), which in turn were significantly larger than pups gestated by control recipients (P < 0.01).     

Observations related to chronologic and gynecologic age in pregnant adolescents.

A low chronologic age (less than or equal to 15 years) and low gynecologic age (less than or equal to 2 years) have been considered factors that increase medical complications among adolescent pregnant women. Gynecologic age (GA) is defined in this study as age in years at conception minus age at menarche. Two hundred twelve consecutive pregnant teenagers were followed prospectively in the Teen OB Clinic at the University of California, San Diego Medical Center, between August 1978 and July 1981. The clinic population consisted of 37.3 percent Whites, 35.8 percent Hispanics, 20.8 percent Blacks, and 6.1 percent other (mostly Indochinese). Sixty-eight percent of the patients were funded by MediCal. The patient population was divided by chronological age (CA) at conception into those 15 years or less or 16 years or older. A low chronological age was found to be a significant risk factor for premature rupture of membranes. Teenagers with a low gynecologic age (less than or equal to 2) had a lower mean pre-pregnancy weight and body mass index (Kg/M2) than teenagers with a higher gynecologic age. In this study, we did not find that a low CA or GA was correlated with a higher frequency of pregnancy-induced hypertension, prenatal medical problems, obstetrical problems at labor or delivery, or an excessive number of low-birthweight infants.     

Are preterm black infants larger than preterm white infants, or are they more misclassified?

In birth certificate data for Massachusetts resident births from 1978 to 1982, 12-27% of births purportedly under 31 weeks of gestation were probably misclassified, i.e. had birthweight greater than or equal to 2500 g. Correcting for maldistribution of births removed 34% and 23%, respectively, of black and white births with reported gestational ages less than 36 weeks but with implausible weights. Percentages of unknown and incomplete reports of last menstrual period were also significantly higher for blacks. After adjustment, preterm black infants weighed less than whites at each gestational age. The proportion of infants less than 2500 g born at term (greater than or equal to 37 weeks gestation) was higher (although not significantly) among blacks. These findings are consistent with hypotheses that low socioeconomic status negatively affects the rate of intrauterine growth.     

Body mass change in breeding Common Terns Sterna hirundo

In 1991–1993 we studied the body mass change of adult Common Terns Sterna hirundo breeding on the German North Sea coast. In each year females' body mass increase prior to laying was very similar (about 5.4 g day^-1). This mass increase resulted in an average body mass of about 175 g on the day of egg-laying. In 1992 and 1993 the females' body mass decreased significantly during incubation, while males' body mass was constant. In 1991, however, neither sex showed a decrease in body mass while incubating. In all years, incubating females and males were heavier than chick-rearing parents. This difference was not caused by higher mass in early incubation, because males and females were still significantly heavier in the last week of incubation than in the first week of chick-rearing. Decreasing mass during incubation and the low body masses during chick-rearing are considerd to be stress induced rather than an adaptive strategy to lower flight costs. The decrease in female body mass during incubation in 1992 and 1993 and the lower body mass of males in these years could be related to less favourable foraging conditions compared to 1991, when both males and females showed the highest average body mass values of the 3 years.     

Birth weight from pregnancies dated by ultrasonography in a multicultural British population.

OBJECTIVE--To produce standard curves of birth weight according to gestational age validated by ultrasonography in the British population, with particular reference to the effects of ethnic origin. DESIGN--Retrospective analysis of computerised obstetric database. SETTING--Three large maternity units associated with Nottingham University with over 16,000 deliveries a year. PATIENTS--41,718 women with ultrasound dated singleton pregnancies and delivery between 168 and 300 days'' gestation. MAIN OUTCOME MEASURES--Length of gestation, ethnic origin, parity, maternal height and weight at booking, smoking during pregnancy; the effect of these variables on birth weight. RESULTS--Birth weights from ultrasound dated pregnancies have a higher population mean and show less flattening of the birthweight curve at term than those of pregnancies dated from menstrual history. Significant differences were observed in mean birth weights of babies of mothers of European origin (3357 g), of Afro-Caribbean origin (3173 g), and from the Indian subcontinent (3096 g). There were also significant interethnic differences in length of gestation, parity, maternal height, booking weight, and smoking habit which affected birth weight. The ethnic differences in birth weight were even greater when the effect of smoking was excluded. CONCLUSIONS--Birthweight standards require precise dating of pregnancy and should describe the population from which they were derived. In a heterogeneous maternity population the accurate assessment of an individual baby''s weight needs to take the factors which affect birthweight standards into consideration.