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Maternal/fetal genetic constitution and environmental factors are vital to delivery of a healthy baby. In the United States (US), a low birth weight (LBW) baby is born every minute and a half. LBW, defined as weighing less than 5.5 lbs at birth, affects nearly 1 in 12 infants born in the US with resultant costs for the nation of more than 15 billion dollars annually. Infant birth weight is the single most important factor affecting neonatal mortality. Various environmental and genetic risk factors for LBW have been identified. Several risks are preventable, such as cigarette smoking during pregnancy. Over one million babies are exposed prenatally to cigarette smoke accounting for over 20% of the LBW incidence in the US. Cigarette smoke exposure in utero results in a variety of adverse developmental outcomes with intrauterine growth restriction and infant LBW being the most well documented. However, the mechanisms underlying the causes of LBW remain poorly understood. The purpose of this study was: (1) to establish an animal model of cigarette smoke-induced in utero growth retardation and LBW using physiologically relevant inhalation exposure conditions which simulate “active” and “passive” tobacco smoke exposures, and (2) to determine whether particular stages of development are more susceptible than others to the adverse effects of in utero smoke exposure on embryo/fetal growth. Pregnant C57BL/6J mice were exposed to cigarette smoke during three periods of gestation: pre-/peri-implantation (gestational days [gds] 1−5), post-implantation (gds 6−18), and throughout gestation (gds 1−17). Reproductive and fetal outcomes were assessed on gd 18.5. Exposure of dams to mainstream/sidestream cigarette smoke, simulating “active” maternal smoking, resulted in decreases in fetal weight and crown–rump length when exposed throughout gestation (gds 1−17). Similar results were seen when dams were exposed only during the first 5 days of gestation (pre-/peri-implantation period gds 1−5). Exposure of dams from the post-implantation period through gestation (gds 6−18) did not result in reduced fetal weight, although a significant reduction in crown–rump length remained evident. Interestingly, maternal sidestream smoke exposure, simulating exposure to environmental tobacco smoke (ETS), during the pre-/peri-implantation period of development also produced significant decreases in fetal weight and crown–rump length. Collectively, results from the present study confirm an association between prenatal exposure to either “active” or “passive” cigarette smoke and in utero growth retardation. The data also identify a period of susceptibility to in utero cigarette smoke exposure-induced growth retardation and LBW during pre-/peri-implantation embryonic development.

The authors evaluated the association between gestational age, birth weight, intrauterine growth and epilepsy in a population-based cohort of 1.4 million singletons born in Denmark (1979-2002). A total of 14,334 individuals were registered with epilepsy in the Danish National Hospital Register as inpatients (1979-2002) and outpatients (1995-2002). Information on gestational age and birth weight was obtained from Danish Medical Birth Registry. Children small at birth were identified through two methods: 1) sex-, birth order-, and gestational-age-specific z-score, and 2) deviation from the expected birth weight estimated based on the birth weight of an older sibling. The incidence rates of epilepsy increased consistently with decreasing gestational age and birth weight. The incidence rate ratios (IRR) for epilepsy in the first year of life were more than five-fold in children born at 22-32 weeks compared with children born at 39-41 weeks, and in children with a birth weight <2,000 grams compared with children of 3,000-3,999 grams. The IRRs decreased with age, but remained elevated into early adulthood. Children identified as growth-restricted according to either of the two methods had increased IRRs for epilepsy, even among children with a ‘normal’ birth weight of 3,500-3,999 grams. Low gestational age at birth and low birth weight are associated with an increased risk of epilepsy throughout childhood and persisting into puberty. Intrauterine growth restriction is associated with an increased risk of epilepsy, even among children with a birth weight in a normal range.

Background

Infant mortality has traditionally been analyzed as a function of birth weight and birth weight-specific mortality. Often, however, when comparing two populations, the population with higher overall mortality has lower mortality at low birth weights and a reversed pattern at higher birth weights. Methods standardizing birth weight, such as the "relative birth weight", have been proposed to eliminate these crossover effects, but such methods do not account for the separate contributions to birth weight of gestational age and fetal "growth."

Methods

Using data for singleton U.S. Blacks (n = 3,683,572) and Whites (n = 18,409,287), we compared neonatal mortality, gestational age, and the difference between the observed birth weight and the optimal birth weight (the weight at which neonatal mortality was lowest) among Black and White infants at the same relative birth weight.

Results

At relative birth weights below zero, gestational ages were, on average, 2.4 ± 1.5 (mean ± standard deviation) weeks shorter for Blacks than for Whites for the same relative birth weight. At relative birth weights above zero, no differences were observed in gestational age, but the optimal birth weight occurred at a much higher relative birth weight in Whites than in Blacks (4150 vs. 3550 g).

Conclusions

Our results suggest that comparisons of neonatal mortality between groups using "relative" birth weight may be potentially biased by differences in gestational age at low birth weights, and by the distance from the optimal birth weight at higher birth weights.

Background

Weight at birth is a good indicator of the newborn's chances for survival, growth, long-term health and psychosocial development. Low birth weight (LBW) babies are significantly at risk of death, contributing to the high perinatal morbidity and mortality in developing countries. Hence, this study aims to assess the incidence and associated factors of low birth weight (LBW) in Gondar University Hospital deliveries.

Methods

A cross-sectional study, conducted on 305 live births from May 1- July 30, 2010. Information on independent variables was collected from the mothers just before discharge using a structured interview questionnaire. Neonatal weight was measured using standard beam balance. Both interviews and weight measurements were done by two trained midwives. Gestational age was determined by last normal menstrual period and/or ultrasound examinations.

Results

The mean and standard deviations of the birth weights were 2976 ±476 grams. Incidence of LBW (birth weight <2500 grams) was 17.1% (95%CI 13.3%, 21.6%). LBW was associated with first delivery (AOR=2.85), lack of antenatal care follow up (AOR= 5.68) or infrequent visits and being HIV positive (AOR=3.22). More female newborns were with low birth weight than males though the difference was not significant after controlling for potential confounders in the multivariate analysis.

Conclusion

There is a high incidence of LBW. Efforts should to enhance national antenatal care utilization in general, and particularly in Gondar, should be encouraged as its absence is closely associated with LBW.

Background

Pregnancies complicated by abnormal umbilical artery Doppler blood flow patterns often result in the baby being born both preterm and growth-restricted. These babies are at high risk of milk intolerance and necrotising enterocolitis, as well as post-natal growth failure, and there is no clinical consensus about how best to feed them. Policies of both early milk feeding and late milk feeding are widely used. This randomised controlled trial aims to determine whether a policy of early initiation of milk feeds is beneficial compared with late initiation. Optimising neonatal feeding for this group of babies may have long-term health implications and if either of these policies is shown to be beneficial it can be immediately adopted into clinical practice.

Methods and Design

Babies with gestational age below 35 weeks, and with birth weight below 10th centile for gestational age, will be randomly allocated to an "early" or "late" enteral feeding regimen, commencing milk feeds on day 2 and day 6 after birth, respectively. Feeds will be gradually increased over 9-13 days (depending on gestational age) using a schedule derived from those used in hospitals in the Eastern and South Western Regions of England, based on surveys of feeding practice. Primary outcome measures are time to establish full enteral feeding and necrotising enterocolitis; secondary outcomes include sepsis and growth. The target sample size is 400 babies. This sample size is large enough to detect a clinically meaningful difference of 3 days in time to establish full enteral feeds between the two feeding policies, with 90% power and a 5% 2-sided significance level. Initial recruitment period was 24 months, subsequently extended to 38 months.

Discussion

There is limited evidence from randomised controlled trials on which to base decisions regarding feeding policy in high risk preterm infants. This multicentre trial will help to guide clinical practice and may also provide pointers for future research.

Trial registration

Current Controlled Trials ISRCTN: 87351483

Background

Maternal weight and maternal weight gain during pregnancy exert a significant influence on infant birth weight and the incidence of macrosomia. Fetal macrosomia is associated with an increase in both adverse obstetric and neonatal outcome, and also confers a future risk of childhood obesity. Studies have shown that a low glycaemic diet is associated with lower birth weights, however these studies have been small and not randomised [1,2]. Fetal macrosomia recurs in a second pregnancy in one third of women, and maternal weight influences this recurrence risk [3].

Methods/Design

We propose a randomised control trial of low glycaemic index carbohydrate diet vs. no dietary intervention in the prevention of recurrence of fetal macrosomia.

Secundigravid women whose first baby was macrosomic, defined as a birth weight greater than 4000 g will be recruited at their first antenatal visit.

Patients will be randomised into two arms, a control arm which will receive no dietary intervention and a diet arm which will be commenced on a low glycaemic index diet.

The primary outcome measure will be the mean birth weight centiles and ponderal indices in each group.

Discussion

Altering the source of maternal dietary carbohydrate may prove to be valuable in the management of pregnancies where there has been a history of fetal macrosomia. Fetal macrosomia recurs in a second pregnancy in one third of women. This randomised control trial will investigate whether or not a low glycaemic index diet can affect this recurrence risk.

Current Controlled Trials Registration Number

ISRCTN54392969

Background

Neonatal mortality because of low birth weight or prematurity remains high in many developing country settings. This research aimed to estimate the sensitivity and specificity, and the positive and negative predictive values of newborn foot length to identify babies who are low birth weight or premature and in need of extra care in a rural African setting.

Methods

A cross-sectional study of newborn babies in hospital, with community follow-up on the fifth day of life, was carried out between 13 July and 16 October 2009 in southern Tanzania. Foot length, birth weight and gestational age were estimated on the first day and foot length remeasured on the fifth day of life.

Results

In hospital 529 babies were recruited and measured within 24 hours of birth, 183 of whom were also followed-up at home on the fifth day. Day one foot length <7 cm at birth was 75% sensitive (95%CI 36-100) and 99% specific (95%CI 97-99) to identify very small babies (birth weight <1500 grams); foot length <8 cm had sensitivity and specificity of 87% (95%CI 79-94) and 60% (95%CI 55-64) to identify those with low birth weight (<2500 grams), and 93% (95%CI 82-99) and 58% (95%CI 53-62) to identify those born premature (<37 weeks). Mean foot length on the first day was 7.8 cm (standard deviation 0.47); the mean difference between first and fifth day foot lengths was 0.1 cm (standard deviation 0.3): foot length measured on or before the fifth day of life identified more than three-quarters of babies who were born low birth weight.

Conclusion

Measurement of newborn foot length for home births in resource poor settings has the potential to be used by birth attendants, community volunteers or parents as a screening tool to identify low birth weight or premature newborns in order that they can receive targeted interventions for improved survival

Background

Sub-Saharan Africa has the highest rates of maternal and neonatal mortality worldwide. Young maternal age at delivery has been proposed as risk factor for adverse pregnancy outcome, yet there is insufficient data from Sub-Saharan Africa. The present study aimed to investigate the influence of maternal adolescence on pregnancy outcomes in the Central African country Gabon.

Methodology and Principal Findings

Data on maternal age, parity, birth weight, gestational age, maternal Plasmodium falciparum infection, use of bednets, and intake of intermittent preventive treatment of malaria in pregnancy were collected in a cross-sectional survey in 775 women giving birth in three mother-child health centers in Gabon. Adolescent women (≤16 years of age) had a significantly increased risk to deliver a baby with low birth weight in univariable analysis (22.8%, 13/57, vs. 9.3%, 67/718, OR: 2.9, 95% CI: 1.5–5.6) and young maternal age showed a statistically significant association with the risk for low birth weight in multivariable regression analysis after correction for established risk factors (OR: 2.7; 95% CI: 1.1–6.5). In further analysis adolescent women were shown to attend significantly less antenatal care visits than adult mothers (3.3±1.9 versus 4.4±1.9 mean visits, p<0.01, n = 356) and this difference accounted at least for part of the excess risk for low birth weight in adolescents.

Conclusion

Our data demonstrate the importance of adolescent age as risk factor for adverse pregnancy outcome. Antenatal care programs specifically tailored for the needs of adolescents may be necessary to improve the frequency of antenatal care visits and pregnancy outcomes in this risk group in Central Africa.

Background

Infants born to diabetic women have certain distinctive characteristics, including large size and high morbidity risks. The neonatal mortality rate is over five times that of infants of non diabetic mothers and is higher at all gestational ages and birth weight for gestational age (GA) categories.

The study aimed to determine morbidity and mortality pattern amongst infants of diabetic mothers (IDMS) admitted into the Special Care Baby Unit of University of Port Harcourt Teaching Hospital.

Methods

This was a study of prevalence of morbidity and mortality among IDMs carried out prospectively over a two year period. All IDMs (pregestational and gestational) admitted into the Unit within the period were recruited into the study.

Data on delivery mode, GA, birth weight, other associated morbidities, investigation results, treatment, duration of hospital stay and outcome were collated and compared with those of infants of non diabetic mothers matched for GA and birth weight admitted within the same period. Maternal data were reviewed retrospectively. Data were analyzed using SPSS 16.0.

Results

Sixty percent of the IDMs were born to mothers with gestational diabetes, while 40% were born to mothers with pregestational DM. 38 (74.3%) were born by Caesarian section (CS), of which 20 (52.6%) were by emergency CS. There was no significant difference in emergency CS rates, when compared with controls, but non-IDMs were more likely to be delivered vaginally. The mean GA of IDMs was 37.84 weeks ± 1.88. 29 (61.7%) of them were macrosomic. The commonest morbidities were Hypoglycemia (significantly higher in IDMs than non-IDMs) and hyperbilirubinaemia in 30 (63.8%) and 26 (57.4%) respectively.

There was no difference in morbidity pattern between infants of pre- gestational and gestational diabetic mothers. Mortality rate was not significantly higher in IDMs

Conclusions

The incidence of macrosomia in IDMs was high but high rates of emergency CS was not peculiar to them. Hypoglycaemia and hyperbilirubinaemia were the commonest morbidities in IDMs.

Referring women with unstable metabolic control to specialized centers improves pre- and post- natal outcomes. Maternal-Infant centers for management of diabetes in pregnancy are advocated on a national scale to reduce associated morbidity and mortality

Thirty-eight ill and premature babies with a diagnosis of persistent ductus arteriosus (PDA) are described. All were patients in the Neonatal Unit of Hammersmith Hospital. 16 of them, who were born during a year in which all babies in the Unit were examined repeatedly and specifically for clinical evidence of PDA, have been compared to a control group in respect of sex, gestational age, weight for dates, birth asphyxia, and respiratory distress.

It is concluded that PDA in this selected group of babies was significantly associated with female sex and respiratory distress but not with gestational age, weight for dates, or birth asphyxia.

Though in these babies clinical evidence of PDA often persisted for several weeks, closure was spontaneous in the great majority.

Five babies developed heart failure and 4 of these responded well to medical treatment. It is suggested that in view of the frequency of spontaneous closure there is no indication to administer oxygen-enriched air to premature babies solely for the purpose of encouraging their ductuses to close.

Objectives: To investigate the relation between the timing of birth and the occurrence of death related to an intrapartum event.

Design: Analysis of 107 206 births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of neonatal death identified in the all Wales perinatal survey, the cause of death classified with the clinicopathological system.

Subjects: 79 normally formed babies stillborn or who died in the neonatal period, birth weight >1499 g, for whom cause of death was related to an intrapartum event.

Main outcome measures: Relative risk of death due to an intrapartum event according to the hour, day, and month of birth.

Results: Mortality was higher in babies born between 9 00 pm and 8 59 am than in those born between 9 00 am and 8 59 pm; relative risk (95% confidence interval) 2.18 (1.37 to 3.47). July and August births also had a higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23). Weekend births had a higher death rate but it was not significant.

Conclusions: The excess of deaths at night and during months when annual leave is popular may indicate an overreliance on inexperienced staff at these times. Errors of judgment may also be related to physical and mental fatigue, demanding a more disciplined systematic approach at night. Mistakes may be ameliorated by increasing shiftwork, but shifts should be carefully designed to avoid undue disruption of circadian rhythms. In addition, greater supervision by senior staff may be required at night and during summer months.

Key messages In low risk pregnancies the incidence of death due to intrapartum asphyxia is regarded as a sensitive measure of the quality of perinatal care Babies born at night and during summer months are at increased risk of death due to intrapartum asphyxia, raising concerns about variability in care around the time of delivery Errors of judgment may be related to mental fatigue. Staff need to be aware of how their performance may vary, and a more disciplined systematic approach at night may be needed Greater supervision by senior staff may be required at night and during summer months

Over a three year period 444 requests for the neonatal transfer of babies with acute medical problems were received at this regional neonatal medical unit. Despite an increase in available resources in the North Western Health Region the provision of intensive care remained inadequate with 38% of requests declined, and babies had to be referred elsewhere including to neighbouring health regions. The survival of those babies who had to remain at the hospital of birth (49%) was significantly lower than for those transferred to the regional centre (71%). Those babies declined admission had significantly lower gestational ages and birth weights than those accepted. For those babies with respiratory failure and birth weights of less than 1500 g within these two groups, however, there were no significant differences in birth weight, gestational age, or gender yet survival was significantly better for those transferred. Babies from multiple pregnancies caused particular problems if neonatal transfer was required.

OBJECTIVE--To determine whether babies in an area of Britain with unusually high perinatal mortality have different patterns of fetal growth to those born elsewhere in the country. DESIGN--Measurement of body size in newborn babies. SETTING--Burnley (perinatal mortality in 1988 15.9/1000 total births) and Salisbury (perinatal mortality 10.8/1000 total births), England. SUBJECTS--Subjects comprised 1544 babies born in Burnley, Pendle, and Rossendale Health District, and 1025 babies born in Salisbury Health District. MAIN OUTCOME MEASURES--Birthweight, length, head, arm and abdominal circumferences, and placental weight were determined. RESULTS--Compared with babies born in Salisbury, Burnley babies had lower mean birthweight (difference 116 g, 95% confidence interval (CI) 77,154), smaller head circumferences (difference 0.3 cm, 95% CI 0.2, 0.4), and were thinner as measured by arm circumference (difference 0.3 cm, 95% CI 0.3, 0.4), abdominal circumference (difference 0.5 cm, 95% CI 0.4, 0.6) and ponderal index (difference 0.8 kg/m3, 95% CI 0.6, 1.0). The ratio of placental weight to birthweight was higher in Burnley (difference 0.6%, 95% CI 0.4, 0.9). These differences were found in boys and girls and did not depend on differences in duration of gestation or on the different ethnic mix of the two districts. Mothers in Burnley were younger, shorter in stature, had had more children, were of lower social class, and more of them smoked during pregnancy than mothers in Salisbury. These differences did not explain the greater thinness of their babies. CONCLUSIONS--Babies born in Burnley, an area with high perinatal mortality, are thin. The reason is unknown. Poor maternal nutrition is suspected because Burnley babies have a higher ratio of placental weight to birthweight. The greater thinness at birth of Burnley babies could have long term consequences, including higher rates of cardiovascular disease.

Background

Neonatal mortality rates among black infants are lower than neonatal mortality rates among white infants at birth weights <3000 g, whereas white infants have a survival advantage at higher birth weights. This finding is also observed when birth weight-specific neonatal mortality rates are compared between infants of smokers and non-smokers. We provide a parsimonious explanation for this paradoxical phenomenon.

Methods

We used data on births in the United States in 1997 after excluding those with a birth weight <500 g or a gestational age <22 weeks. Birth weight- and gestational age-specific perinatal mortality rates were calculated per convention (using total live births at each birth weight/gestational age as the denominator) and also using the fetuses at risk of death at each gestational age.

Results

Perinatal mortality rates (calculated per convention) were lower among blacks than whites at lower birth weights and at preterm gestational ages, while blacks had higher mortality rates at higher birth weights and later gestational ages. With the fetuses-at-risk approach, mortality curves did not intersect; blacks had higher mortality rates at all gestational ages. Increases in birth rates and (especially) growth-restriction rates presaged gestational age-dependent increases in perinatal mortality. Similar findings were obtained in comparisons of smokers versus nonsmokers.

Conclusions

Formulating perinatal risk based on the fetuses-at-risk approach solves the intersecting perinatal mortality curves paradox; blacks have higher perinatal mortality rates than whites and smokers have higher perinatal mortality rates than nonsmokers at all gestational ages and birth weights.

Aim

To identify antenatal and perinatal risk factors for in‐hospital mortality of babies born within the Australian and New Zealand Neonatal Network (ANZNN).

Methods

Data were collected prospectively as part of the ongoing audit of high‐risk infants (birth weight <1500 g or gestation <32 weeks) admitted to all level III neonatal units in Australia and New Zealand. Antenatal and intrapartum factors to 1 min of age were examined in 11 498 infants with gestational age >24 weeks. Risk and protective factors for mortality were derived from logistic regression models fitted to 1998–9 data and validated on 2000–1 data.

Results

For the whole cohort of infants born between 1998 and 2001, prematurity was the dominant risk factor, infants born at 25 weeks having 32 times greater odds of death than infants born at 31 weeks. Low birth weight for gestational age also had a dose–response effect: the more growth restricted the infant the greater the risk of mortality; infants below the 3rd centile had eight times greater odds of death than those between the 25th and 75th centiles. Male sex was also a significant risk factor (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.31 to 1.82). Maternal hypertension in pregnancy was protective (OR 0.46, 95% CI 0.36 to 0.50). The predictive model for mortality had an area under the receiver operating characteristic curve of 0.82.

Conclusions

Risk of mortality can be predicted with good accuracy with factors up to the 1 min Apgar score. By using gestation rather than birth weight as the main indicator of maturity, these data confirm that weight for gestational age is an independent risk factor for mortality.

Background

Worldwide 15.5% of neonates are born with low birth weight, 95.6% of them in the developing countries. Prematurity accounts for 10% of neonatal mortality globally. The purpose of this study was to evaluate the effects of birth weight and gender on neonatal outcome.

Findings

The data of 278 neonates managed in the Special Care Baby Unit (SCBU) of Jos University Teaching Hospital (JUTH) over a 2 year period from July 2006 to June 2008 were analyzed.

One hundred and fifty nine (57.2%) were males and 119(42.8%) females. There were 87(31.3%) preterm and 191 (68.7%) term babies. Twelve of the babies died. Seven (2.52%) and 5 (1.80%) being males and females respectively. The neonatal mortality rate by gender was not significant (p > 0.05). The neonatal mortality was 25.2 deaths per 1000 live births for boys and 18.0 for girls. The mean birth weights of the preterm and term babies were 1.88 ± 0.47 kg and 3.02 ± 0.50 kg respectively, with a mean gestational age of 30.62 ± 3.65 weeks and 38.29 ± 0.99 weeks respectively.

Eighty seven (31.3%) of the babies were of low birth weight, 188(67.6%) were of normal birth weight and 3(1.1%) high birth weight. Of the low birth weight babies, 6(2.2%) were term small for gestational age. Six (2.2%) of the preterm infants had normal birth weight.

Eleven of the babies that died were preterm low birth weight. The overall mortality rate was 4.32%. The birth weight specific mortality rate was 126 per 1000 for the preterm low birth weight and 5 per 1000 for the term babies. Birth weight unlike gender is a significant predictor of mortality, mortality being higher in neonates of <2.5 kg (OR = 0.04; 95% Cl 0.005-0.310, p = 0.002) (p = 0.453). Seven (58.3%) and 4(33.3%) of the pre-terms that died were appropriate and large for gestational age respectively. Gestational age is not a significant predictor of neonatal mortality (p = 0.595). Babies delivered at less than 37 weeks of gestation recorded a higher rate of mortality than those of 37 weeks and above (p = 0.000).

The subjects showed one or more major clinical indications for admission. The major clinical indications for the preterm and term babies were respectively as follows: neonatal sepsis 63(22.7%) and 124(44.6%); neonatal jaundice 32(11.1%) and 71(24.7%); malaria 9(3.1%) and 13(4.5%); birth asphyxia 3(1.0%) and 7(2.4%). Neonatal sepsis was a common denominator among the babies that died.

Conclusion

Birth weight unlike gender is a significant predictor of neonatal outcome

Background

Small for gestational age neonates have a higher risk of growth delay. The purpose of the study is to determine if there are differences in their early weight gain patterns that persist after adjusting for confounding variables.

Methods

Two-hundred sixteen neonates born between 1999 and 2003 were included. The group for analysis was derived by matching all the SGA infants with AGA infants by sex, year of birth, and birth weight. The period of observation was from birth to date of discharge. Weight gain rate was defined as grams gained per kilogram of birth weight per day. Two sample T-test was used to determine the difference in growth rate between the groups. Simple regression was used to establish the effect of morbidities on weight gain rate.

Results

The total mean birth weight was 1105 g (± 223 g), the mean gestational age was 30 weeks (± 2.7 weeks), and the mean weight gain rate was 13.4 g/kg/d (± 6.8 g/kg/d). The mean weight gain rate for the adequate for gestational age group was lower (11.9 g/kg/d ± 7.6g versus 14.9 g/kg/d ± 5.5g) (P<0.001). When all variables were analyzed using the lineal regression model, only having a low APGAR score (P=0.02) and being small for gestational age (P=0.0004) were significant.

Conclusions

We conclude that the growth patterns of very low birth weight neonates are different based on the adequacy of their birth weight, and that the disparity in growth rate is not explained by the differences in the incidence of morbidities that affect growth.

Background

Low birth weight (<2,500 g) is a strong predictor of infant mortality. Yet low birth weight, in isolation, is uninformative since it is comprised of two intertwined components: preterm delivery and reduced fetal growth. Through nonparametric logistic regression models, we examine the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality.

Methods

We derived data on over 10 million singleton live births delivered at ≥ 24 weeks from the 1998–2000 U.S. natality data files. Nonparametric multivariable logistic regression based on generalized additive models was used to examine neonatal mortality (deaths within the first 28 days) in relation to fetal growth (gestational age-specific standardized birth weight), gestational age, and number of cigarettes smoked per day. All analyses were further adjusted for the confounding effects due to maternal age and gravidity.

Results

The relationship between standardized birth weight and neonatal mortality is nonlinear; mortality is high at low z-score birth weights, drops precipitously with increasing z-score birth weight, and begins to flatten for heavier infants. Gestational age is also strongly associated with mortality, with patterns similar to those of z-score birth weight. Although the direct effect of smoking on neonatal mortality is weak, its effects (on mortality) appear to be largely mediated through reduced fetal growth and, to a lesser extent, through shortened gestation. In fact, the association between smoking and reduced fetal growth gets stronger as pregnancies approach term.

Conclusions

Our study provides important insights regarding the combined effects of fetal growth, gestational age, and smoking on neonatal mortality. The findings suggest that the effect of maternal smoking on neonatal mortality is largely mediated through reduced fetal growth.

Contemporary fetal growth standards are created by using theoretical properties (percentiles) of birth weight (for gestational age) distributions. The authors used a clinically relevant, outcome-based methodology to determine if separate fetal growth standards are required for singletons and twins. All singleton and twin livebirths between 36 and 42 weeks’ gestation in the United States (1995–2002) were included, after exclusions for missing information and other factors (n = 17,811,922). A birth weight range was identified, at each gestational age, over which serious neonatal morbidity and neonatal mortality rates were lowest. Among singleton males at 40 weeks, serious neonatal morbidity/mortality rates were lowest between 3,012 g (95% confidence interval (CI): 3,008, 3,018) and 3,978 g (95% CI: 3,976, 3,980). The low end of this optimal birth weight range for females was 37 g (95% CI: 21, 53) less. The low optimal birth weight was 152 g (95% CI: 121, 183) less for twins compared with singletons. No differences were observed in low optimal birth weight by period (1999–2002 vs. 1995–1998), but small differences were observed for maternal education, race, parity, age, and smoking status. Patterns of birth weight-specific serious neonatal morbidity/neonatal mortality support the need for plurality-specific fetal growth standards.

OBJECTIVES

The objective of this study was to determine the (1) incidence of short bowel syndrome in very low birth weight (<1500 g) infants, (2) associated morbidity and mortality during initial hospitalization, and (3) impact on short-term growth and nutrition in extremely low birth weight (<1000 g) infants.

METHODS

Infants who were born from January 1, 2002, through June 30, 2005, and enrolled in the National Institute of Child Health and Human Development Neonatal Research Network were studied. Risk factors for developing short bowel syndrome as a result of partial bowel resection (surgical short bowel syndrome) and outcomes were evaluated for all neonates until hospital discharge, death, or 120 days. Extremely low birth weight survivors were further evaluated at 18 to 22 months’ corrected age for feeding methods and growth.

RESULTS

The incidence of surgical short bowel syndrome in this cohort of 12 316 very low birth weight infants was 0.7%. Necrotizing enterocolitis was the most common diagnosis associated with surgical short bowel syndrome. More very low birth weight infants with short bowel syndrome (20%) died during initial hospitalization than those without necrotizing enterocolitis or short bowel syndrome (12%) but fewer than the infants with surgical necrotizing enterocolitis without short bowel syndrome (53%). Among 5657 extremely low birth weight infants, the incidence of surgical short bowel syndrome was 1.1%. At 18 to 22 months, extremely low birth weight infants with short bowel syndrome were more likely to still require tube feeding (33%) and to have been rehospitalized (79%). Moreover, these infants had growth delay with shorter lengths and smaller head circumferences than infants without necrotizing enterocolitis or short bowel syndrome.

CONCLUSIONS

Short bowel syndrome is rare in neonates but has a high mortality rate. At 18 to 22 months’ corrected age, extremely low birth weight infants with short bowel syndrome were more likely to have growth failure than infants without short bowel syndrome.

Introduction

It is debated whether teenage pregnancy is associated with an adverse reproductive outcome. This study assessed the reproductive outcomes in teenage pregnancy in Nepal, a developing setting.

Methods

A hospital based retrospective cohort study of 4,101 deliveries to compare the outcomes between teenage and non-teenage pregnancies.

Results

Pregnancy in teenagers was associated with significantly increased risk (P<0.05) of delivery of very and moderately preterm births and Low Birth Weight babies. There was no significant difference in risk of having small for gestational age babies, low APGAR score at birth at 1 min and 5 min, stillbirth, neonatal death, and post partum hemorrhage. However, the risk of having delivery by episiotomy, vacuum or forceps and Caesarean section was significantly lower (P<0.05) among teenage mothers.

Conclusion

Teenage women were more likely to have preterm births and low birth weight babies. However, they were less likely to have delivery by episiotomy, forceps or vacuum and Caesarean sections. In other respects, there were no significant differences between teenage and non-teenage mothers.

A prospective study of 483 pregnant women was undertaken to examine possible associations of social and psychiatric factors with both low birth weight (less than 2500 g) and preterm delivery (less than 37 weeks' gestation). As few babies were born before term (n = 14) or with a low birth weight (n = 14) further analyses were conducted to investigate predictors of absolute birth weight and gestational age. Low income was found to be an independent predictor of birth weight when birth weight was treated both as a dichotomous and as a continuous variable. Unemployment was found to be associated with absolute birth weight. Although this effect was statistically accounted for by low income, a low income was frequently caused by unemployment. Smoking independently predicted absolute birth weight and tended to be associated with preterm delivery. None of the factors investigated was associated with gestational age. In contrast with previous findings, factors such as social class, adverse life events, and psychiatric state were not associated with birth outcome. The mechanism underlying the association between low income and low birth weight requires further investigation.

In an analysis of four datasets from East Africa, Tanya Marchant and colleagues investigate the neonatal mortality risk associated with preterm birth and how this changes with weight for gestational age.

Background

Low birth weight and prematurity are amongst the strongest predictors of neonatal death. However, the extent to which they act independently is poorly understood. Our objective was to estimate the neonatal mortality risk associated with preterm birth when stratified by weight for gestational age in the high mortality setting of East Africa.

Methods and Findings

Members and collaborators of the Malaria and the MARCH Centers, at the London School of Hygiene & Tropical Medicine, were contacted and protocols reviewed for East African studies that measured (1) birth weight, (2) gestational age at birth using antenatal ultrasound or neonatal assessment, and (3) neonatal mortality. Ten datasets were identified and four met the inclusion criteria. The four datasets (from Uganda, Kenya, and two from Tanzania) contained 5,727 births recorded between 1999–2010. 4,843 births had complete outcome data and were included in an individual participant level meta-analysis. 99% of 445 low birth weight (<2,500 g) babies were either preterm (<37 weeks gestation) or small for gestational age (below tenth percentile of weight for gestational age). 52% of 87 neonatal deaths occurred in preterm or small for gestational age babies. Babies born <34 weeks gestation had the highest odds of death compared to term babies (odds ratio [OR] 58.7 [95% CI 28.4–121.4]), with little difference when stratified by weight for gestational age. Babies born 34–36 weeks gestation with appropriate weight for gestational age had just three times the likelihood of neonatal death compared to babies born term, (OR 3.2 [95% CI 1.0–10.7]), but the likelihood for babies born 34–36 weeks who were also small for gestational age was 20 times higher (OR 19.8 [95% CI 8.3–47.4]). Only 1% of babies were born moderately premature and small for gestational age, but this group suffered 8% of deaths. Individual level data on newborns are scarce in East Africa; potential biases arising due to the non-systematic selection of the individual studies, or due to the methods applied for estimating gestational age, are discussed.

Conclusions

Moderately preterm babies who are also small for gestational age experience a considerably increased likelihood of neonatal death in East Africa.

Please see later in the article for the Editors' Summary.

Editors' Summary

Background

Worldwide, every year around 3.3 million babies die within their first month of life and the proportion of under-five child deaths that are now in the neonatal period (the first 28 days of life) has increased in all regions of the world and is currently estimated at 41%. Of these deaths, over 90% occur in low- and middle-income countries, and a third of all neonatal deaths occur in sub-Saharan Africa. Low birth weight (defined as <2,500 g) is one of the biggest risk factors associated with neonatal deaths but it is the causes of low birth weight, rather than the low weight itself that is thought to lead to neonatal deaths. The two main causes of low birth weight are preterm birth (delivery before 37 weeks gestation) and/or restricted growth in the womb (intra-uterine growth retardation), resulting in babies who are small for their dates (defined as being in the lowest 10% of weight expected for gestational age with reference to a US population).

Why Was This Study Done?

Despite growing international attention focused on neonatal mortality in recent years, the relative importance of low birth weight, small for gestational age, and preterm birth in causing newborn deaths remains unclear. So in this study, the researchers investigated these relationships by calculating the risk of neonatal mortality associated with preterm birth after adjusting for weight for gestational age by conducting a meta-analysis (synthesis of the data) using information from studies reporting neonatal mortality conducted in sub-Saharan Africa.

What Did the Researchers Do and Find?

The researchers identified potential African datasets and selected four out of a possible ten to include in their analysis as these studies included three essential birth outcomes: birth weight; gestational age measured using antenatal ultrasound, or neonatal assessment on the day of birth; and neonatal mortality. These four studies were conducted in Kenya, Tanzania, and Uganda, all in East Africa. The researchers analysed each study separately but also conducted a pooled statistical analysis on all four studies. To give a more detailed analysis, the researchers categorized babies into six groups taking into account whether the babies were moderately preterm (born at 34–36 weeks) or very preterm (born before 34 weeks) and whether their weight was appropriate for their gestational age.

The researchers included a total of 4,843 live births in their analysis and found that overall, 9.2% of babies were low birth weight, 4.0% were preterm, and 20.4% were small for gestational age. Amongst low birth weight babies, 26.1% were preterm, 85.0% were small for gestational age, and 98.8% were either preterm or small for gestational age. In their detailed analysis, the researchers found that the odds (chance) of death in the first 28 days of life were seven times higher for babies born low birth weight compared to those with normal birth weight, with low birth weight infants experiencing a neonatal mortality rate of 80.9/1,000 live births. The odds of death were twice as high for babies born small for gestational age compared to those born appropriate for gestational age, giving a neonatal mortality rate of 29.3/1,000 live births. Furthermore, compared to those born at term, the odds of death were over six times higher for babies born moderately preterm and almost 60 times higher for babies born very preterm with almost half of all very preterm babies dying in the first 28 days of life, giving a neonatal mortality rate 473.6/1,000 live births. However, moderately preterm babies who were small for gestational age had a much greater odds of death than moderately preterm babies who were of the appropriate weight for their gestational age.

What Do These Findings Mean?

These findings from East Africa show that babies born either small for gestational age or preterm contributed 52% of neonatal deaths. The detailed analysis suggests that babies born preterm are at the greatest risk of death, but size for gestational age also plays an important role especially in moderately preterm babies. The results from this study emphasize the pressing need to find ways to prevent preterm delivery and intra-uterine growth retardation and also illustrate the importance of measuring and reporting outcomes of individual babies.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001292.

A recent PLOS Medicine study by Oestergaard et al. has the latest global figures on neonatal mortality

UNICEF provides information on neonatal mortality

The World Health Organization (WHO) provides factsheets on the causes of neonatal mortality, including preterm birth

Background

The use of bovine in vitro embryo production (IVP) increases the reproductive potential of genetically superior cows, enabling a larger scale of embryo production when compared with other biotechnologies. However, deleterious effects such as abnormal fetal growth, longer gestation period, increased birth weight, abortion, preterm birth and higher rates of neonatal mortality have been attributed to IVP. The aim of this study was to compare the influence of in vitro embryo production and artificial insemination (AI) on gestation length, complications with birth, birth weight, method of feeding colostrum, passive transfer of immunity, morbidity-mortality, and performance in Brahman calves.

Results

Whilst gestation length and birth weight were significantly increased in IVP-derived calves, no difference in weaning weight was observed between groups. The passive transfer of immunity (PT), was assessed in IVP (n = 80) and AI (n = 20) groups 24 hours after birth by determination of gamma-glutamyl transferase (GGT) and gammaglobulin activity as well as by quantification of the concentration of total protein in serum. No differences in passive transfer or incidences of dystocia and diseases at weaning were observed between groups. Birth weight, method of feeding colostrum and dystocia were not correlated with PT in either group.

Conclusions

In this study, in vitro embryo production did not affect the health status, development, or passive transfer of immunity in Brahman calves.

The birth weight/gestation distribution of a large series of cases of perinatal death has been analysed according to the lesion (or lesions) present at necropsy. Among the lesions associated with low gestation babies dying with hyaline membranes have a much higher mean birth weight for gestation than either the babies with intraventricular haemorrhage or “no cause found.” Among infants dying of intrapartum asphyxia or cerebral birth trauma it was found that those who were stillborn with trauma had, at term, a significantly higher mean birth weight than the control livebirths, and that, at all gestations, the stillbirths with trauma were, on average, heavier than the babies dying neonatally with this lesion. Cases of intrapartum asphyxia were smaller than the stillbirths with trauma, but those dying during the second stage of labour were larger than those dying during the first stage.

Cases of intrauterine pneumonia—that is, stillbirths and first-day deaths—were also shown to be larger for length of gestation than cases of extrauterine pneumonia—that is, deaths between the second and the 28th day. The cases with haemorrhagic pneumonia, however, were, at least at term, smaller than the cases of extrauterine pneumonia, and cases of massive pulmonary haemorrhage showed evidence of growth retardation at all gestations.