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1.  Gestational Age, Birth Weight, Intrauterine Growth and Risk for Epilepsy 
American journal of epidemiology  2007;167(3):262-270.
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.
PMCID: PMC2632964  PMID: 18042672
2.  An animal model of cigarette smoke-induced in utero growth retardation 
Toxicology  2008;246(2-3):193-202.
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.
PMCID: PMC2746649  PMID: 18316152
Embryo; Fetus; Pre-implantation; Cigarette smoke; Tobacco; Low birth weight
3.  A randomised control trial of low glycaemic index carbohydrate diet versus no dietary intervention in the prevention of recurrence of macrosomia 
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].
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.
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
PMCID: PMC2876071  PMID: 20416041
4.  Analysis of neonatal mortality:is standardizing for relative birth weight biased? 
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."
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.
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).
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.
PMCID: PMC441380  PMID: 15180905
Birth weight; gestational age; relative birth weight; optimal birth weight
5.  Adolescence As Risk Factor for Adverse Pregnancy Outcome in Central Africa – A Cross-Sectional Study 
PLoS ONE  2010;5(12):e14367.
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.
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.
PMCID: PMC3004789  PMID: 21188301
6.  Referrals to a regional neonatal intensive care unit. 
Archives of Disease in Childhood  1988;63(4):403-407.
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.
PMCID: PMC1778830  PMID: 3365010
7.  Incidence and correlates of low birth weight at a referral hospital in Northwest Ethiopia 
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.
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.
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.
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.
PMCID: PMC3396870  PMID: 22826729
Prevalence; Low Birth Weight; referral hospital; Ethiopia
8.  The effect of IVF pregnancies on mortality and morbidity in tertiary unit 
There are several studies that have shown an increased risk of premature birth and developmental abnormalities with in vitro fertilization (IVF); however, the data on preterm mortality and morbidity are limited.
Our aim is to investigate whether IVF had an effect on the mortality and morbidity in neonates admitted to the neonatal intensive care unit.
A total of 940 term and preterm babies who were admitted to the intensive care unit over a period of 2 years were enrolled. Of these, 121 babies were born after IVF and 810 were born after a natural conception and 9 were born after ovulation induction. Of these, 112 preterm babies were born after IVF and 405 preterm babies were born after a natural conception.
In the IVF group, the gestational age and birth weight were significantly lower than in the non-IVF group. Additionally, in the IVF group, multiple births were significantly higher than in the non-IVF group. IVF pregnancies increase preterm delivery but did not increase preterm mortality, and preterm morbidity did not differ among groups, except for intraventricular hemorrhage (IVH). Gestational age was shown to be the primary risk factor for IVH using a logistic regression analysis. Also when newborns at gestational age <32 weeks were compared using regression analysis, gestational age was the major risk factor for IVH.
IVF appears to be associated with premature delivery and the known risks associated with prematurity.
PMCID: PMC3626728  PMID: 23497498
9.  Biological Rhythms and Preeclampsia 
The impact of impaired circadian rhythm on health has been widely studied in shift workers and trans-meridian travelers. A part from its correlation with sleep and mood disorders, biological rhythm impairment is a recognized risk factor for cardiovascular diseases and breast cancer. Preeclampsia is a major public health issue, associated with a significant maternal and fetal morbidity and mortality worldwide. While the risks factors for this condition such as obesity, diabetes, pre-existing hypertension have been identified, the underlying mechanism of this multi-factorial disease is yet not fully understood. The disruption of the light/dark cycle in pregnancy has been associated with adverse outcomes. Slightly increased risk for “small for gestational age” babies, “low birth weight” babies, and preterm deliveries has been reported in shift working women. Whether altered circadian cycle represents a risk factor for preeclampsia or preeclampsia is itself linked with an abnormal circadian cycle is less clear. There are only few reports available, showing conflicting results. In this review, we will discuss recent observations concerning circadian pattern of blood pressure in normotensive and hypertensive pregnancies. We explore the hypothesis that circadian misalignments may represent a risk factor for preeclampsia. Unraveling potential link between circadian clock gene and preeclampsia could offer a novel approach to our understanding of this multi-system disease specific to pregnancy.
PMCID: PMC3619120  PMID: 23579266
circadian clock; pregnancy; preeclampsia; shift work; women health
10.  Measuring newborn foot length to identify small babies in need of extra care: a cross sectional hospital based study with community follow-up in Tanzania 
BMC Public Health  2010;10:624.
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.
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.
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.
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
PMCID: PMC2975655  PMID: 20959008
11.  Low Birth Weight, Small for Gestational Age and Preterm Births before and after the Economic Collapse in Iceland: A Population Based Cohort Study 
PLoS ONE  2013;8(12):e80499.
Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes.
Study design
The study population constituted all Icelandic women giving birth to live-born singletons from January 1st 2006 to December 31st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD's) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6th 2008.
Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse.
The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation.
PMCID: PMC3851132  PMID: 24324602
12.  Periodontal diseases as an emerging potential risk factor for adverse pregnancy outcomes: A review of concepts 
Preterm birth is the leading perinatal problem with subsequent morbidity and mortality in developed as well as developing nations. Among the various possible environmental, genetic, demographic, psychosocial and obstetric risk factors responsible for premature labor, poor oral health with periodontal infection has also emerged as a potential and modifiable risk factor for preterm low birth weight babies. The infected periodontium is regarded as a reservoir for periodontopathic bacteria, mainly gram negative anaerobes that serve as a source of endotoxins and lipopolysaccharides, proinflammatory cytokines and prostaglandins that enhance uterine muscle contraction leading to preterm low birth weight. Also, the progression of periodontal disease during pregnancy appears to increase the fetal growth restriction, irrespective of baseline periodontal disease status. Thus, identification and treatment of periodontal disease should be considered an important intervention strategy as a part of prenatal care to reduce adverse pregnancy outcomes.
PMCID: PMC3939276  PMID: 24591987
Adverse pregnancy outcomes; periodontal diseases; preterm low birth weight
13.  Intersecting Birth Weight-specific Mortality Curves: Solving the Riddle 
American Journal of Epidemiology  2009;169(7):787-797.
Small babies from a population with higher infant mortality often have better survival than small babies from a lower-risk population. This phenomenon can in principle be explained entirely by the presence of unmeasured confounding factors that increase mortality and decrease birth weight. Using a previously developed model for birth weight-specific mortality, the authors demonstrate specifically how strong unmeasured confounders can cause mortality curves stratified by known risk factors to intersect. In this model, the addition of a simple exposure (one that reduces birth weight and independently increases mortality) will produce the familiar reversal of risk among small babies. Furthermore, the model explicitly shows how the mix of high- and low-risk babies within a given stratum of birth weight produces lower mortality for high-risk babies at low birth weights. If unmeasured confounders are, in fact, responsible for the intersection of weight-specific mortality curves, then they must also (by virtue of being confounders) contribute to the strength of the observed gradient of mortality by birth weight. It follows that the true gradient of mortality with birth weight would be weaker than what is observed, if indeed there is any true gradient at all.
PMCID: PMC2727223  PMID: 19240224
birth weight; confounding factors (epidemiology); infant mortality; smoking
14.  Born Too Soon: The global epidemiology of 15 million preterm births 
Reproductive Health  2013;10(Suppl 1):S2.
This second paper in the Born Too Soon supplement presents a review of the epidemiology of preterm birth, and its burden globally, including priorities for action to improve the data. Worldwide an estimated 11.1% of all livebirths in 2010 were born preterm (14.9 million babies born before 37 weeks of gestation), with preterm birth rates increasing in most countries with reliable trend data. Direct complications of preterm birth account for one million deaths each year, and preterm birth is a risk factor in over 50% of all neonatal deaths. In addition, preterm birth can result in a range of long-term complications in survivors, with the frequency and severity of adverse outcomes rising with decreasing gestational age and decreasing quality of care. The economic costs of preterm birth are large in terms of immediate neonatal intensive care, ongoing long-term complex health needs, as well as lost economic productivity. Preterm birth is a syndrome with a variety of causes and underlying factors usually divided into spontaneous and provider-initiated preterm births. Consistent recording of all pregnancy outcomes, including stillbirths, and standard application of preterm definitions is important in all settings to advance both the understanding and the monitoring of trends. Context specific innovative solutions to prevent preterm birth and hence reduce preterm birth rates all around the world are urgently needed. Strengthened data systems are required to adequately track trends in preterm birth rates and program effectiveness. These efforts must be coupled with action now to implement improved antenatal, obstetric and newborn care to increase survival and reduce disability amongst those born too soon.
This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format.
PMCID: PMC3828585  PMID: 24625129
Preterm birth; epidemiology; neonatal mortality
15.  Morbidity-mortality and performance evaluation of Brahman calves from in vitro embryo production 
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.
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.
In this study, in vitro embryo production did not affect the health status, development, or passive transfer of immunity in Brahman calves.
PMCID: PMC3248837  PMID: 22136315
16.  Adverse Reproductive Outcomes Associated With Teenage Pregnancy 
McGill Journal of Medicine : MJM  2008;11(2):141-144.
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.
A hospital based retrospective cohort study of 4,101 deliveries to compare the outcomes between teenage and non-teenage pregnancies.
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.
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.
PMCID: PMC2582661  PMID: 19148312
Teenage; Pregnancy; Outcome; Preterm; Low Birth Weight; SGA; Caesarean
17.  Refractive Status at Birth: Its Relation to Newborn Physical Parameters at Birth and Gestational Age 
PLoS ONE  2009;4(2):e4469.
Refractive status at birth is related to gestational age. Preterm babies have myopia which decreases as gestational age increases and term babies are known to be hypermetropic. This study looked at the correlation of refractive status with birth weight in term and preterm babies, and with physical indicators of intra-uterine growth such as the head circumference and length of the baby at birth.
All babies delivered at St. Stephens Hospital and admitted in the nursery were eligible for the study. Refraction was performed within the first week of life. 0.8% tropicamide with 0.5% phenylephrine was used to achieve cycloplegia and paralysis of accommodation. 599 newborn babies participated in the study. Data pertaining to the right eye is utilized for all the analyses except that for anisometropia where the two eyes were compared. Growth parameters were measured soon after birth. Simple linear regression analysis was performed to see the association of refractive status, (mean spherical equivalent (MSE), astigmatism and anisometropia) with each of the study variables, namely gestation, length, weight and head circumference. Subsequently, multiple linear regression was carried out to identify the independent predictors for each of the outcome parameters.
Simple linear regression showed a significant relation between all 4 study variables and refractive error but in multiple regression only gestational age and weight were related to refractive error. The partial correlation of weight with MSE adjusted for gestation was 0.28 and that of gestation with MSE adjusted for weight was 0.10. Birth weight had a higher correlation to MSE than gestational age.
This is the first study to look at refractive error against all these growth parameters, in preterm and term babies at birth. It would appear from this study that birth weight rather than gestation should be used as criteria for screening for refractive error, especially in developing countries where the incidence of intrauterine malnutrition is higher.
PMCID: PMC2636866  PMID: 19214228
18.  Trends in birth weight and the prevalence of low birth weight and small-for-gestational-age in Surinamese South Asian babies since 1974: cross-sectional study of three birth cohorts 
BMC Public Health  2013;13:931.
South Asian babies born in developed countries are generally lighter than babies from other ethnic groups born in the same country. While the mean birth weight of Caucasian babies in the Netherlands has increased the past decades, it is unknown if the mean birth weight of South Asian babies born in the Netherlands has increased or if the prevalence of low birth weight (LBW) or small-for-gestational-age (SGA) has decreased.
The aims of this study are: 1. to investigate secular changes in mean birth weight and the prevalence of LBW and SGA in Surinamese South Asian babies, and 2. to assess differences between Surinamese South Asian and Dutch Caucasian neonates born 2006–2009.
A population based study for which neonatal characteristics of 2014 Surinamese South Asian babies, born between 1974 and 2009 in the Netherlands, and 3104 Dutch Caucasian babies born 2006–2009 were obtained from well-baby clinic records. LBW was defined as a birth weight <2500 g. SGA was based on a universal population standard (the Netherlands) and three ethnic specific standards (the Netherlands, UK, Canada).
In Surinamese South Asian babies from 1974 to 2009 no secular trend in mean birth weight and prevalence of LBW was found, whereas SGA prevalence decreased significantly.
Surinamese South Asian babies born in 2006–2009 (2993 g; 95% CI 2959-3029 g) were 450 g lighter than Dutch Caucasian babies (3448 g; 95% CI 3429-3468 g), while LBW and SGA prevalences, based on universal standards, were three times higher. Application of ethnic specific standards from the Netherlands and the UK yielded SGA rates in Surinamese South Asian babies that were similar to Dutch. There were considerable differences between the standards used.
Since 1974, although the mean birth weight of Surinamese South Asian babies remained unchanged, they gained a healthier weight for their gestational age.
PMCID: PMC3851477  PMID: 24098977
Birth weight; Infant, low birth weight; Infant, small for gestational age; India; The Netherlands
19.  A parsimonious explanation for intersecting perinatal mortality curves: understanding the effects of race and of maternal smoking 
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.
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.
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.
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.
PMCID: PMC419704  PMID: 15090071
20.  ADEPT - Abnormal Doppler Enteral Prescription Trial 
BMC Pediatrics  2009;9:63.
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.
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
PMCID: PMC2770036  PMID: 19799788
21.  Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis 
Lancet  2013;382(9890):417-425.
Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and middle-income countries.
For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the third and tenth percentile of a US reference population), and preterm and SGA combinations.
Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with either characteristic alone (15·42; 9·11–26·12).
Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm and SGA rather than with low birthweight could guide prevention and management strategies to speed progress towards Millennium Development Goal 4—the reduction of child mortality.
Bill & Melinda Gates Foundation.
PMCID: PMC3796350  PMID: 23746775
22.  Perinatal factors and adverse outcome in extremely low birthweight infants. 
Archives of Disease in Childhood  1986;61(6):554-558.
Perinatal factors associated with death or disability at 2 years were identified in an inborn cohort of 196 live births with a birth weight of 500-999 g. Antepartum haemorrhage, multiple pregnancy, breech presentation, perinatal asphyxia, hypothermia on admission, hyaline membrane disease, persistent pulmonary hypertension, severe respiratory failure, and intraventricular haemorrhage were associated with increased mortality. Factors associated with increased survival included maternal hypertension, caesarean birth, increasing maturity or size at birth, female sex, and fetal growth retardation. Stepwise multiple discriminant function analysis showed that six factors correctly classified the outcome in 83% of infants: intraventricular haemorrhage was the most important factor followed by the presence of acidosis and hypoxia in the early neonatal period, birth weight, pre-eclamptic toxaemia, and caesarean birth. This study also showed that intraventricular haemorrhage, seizures, antepartum haemorrhage and delay in regaining birth weight were associated with increased disability among survivors.
PMCID: PMC1777856  PMID: 3729524
23.  Theory of obstetrics: An epidemiologic framework for justifying medically indicated early delivery 
Modern obstetrics is faced with a serious paradox. Obstetric practice is becoming increasingly interventionist based on empirical evidence but without a theoretical basis for such intervention. Whereas obstetric models of perinatal death show that mortality declines exponentially with increasing gestational duration, temporal increases in medically indicated labour induction and cesarean delivery have resulted in rising rates of preterm birth and declining rates of postterm birth. Other problems include a disconnection between patterns of gestational age-specific growth restriction (constant across gestation) and gestational age-specific perinatal mortality (exponential decline with increasing duration) and the paradox of intersecting perinatal mortality curves (low birth weight infants of smokers have lower neonatal mortality rates than the low birth weight infants of non-smokers).
The fetuses at risk approach is a causal model that brings coherence to the various perinatal phenomena. Under this formulation, pregnancy complications (such as preeclampsia), labour induction/cesarean delivery, birth, revealed small-for-gestational age and death show coherent patterns of incidence. The fetuses at risk formulation also provides a theoretical justification for medically indicated early delivery, the cornerstone of modern obstetrics. It permits a conceptualization of the number needed to treat (e.g., as low as 2 for emergency cesarean delivery in preventing perinatal death given placental abruption and fetal bradycardia) and a calculation of the marginal number needed to treat (i.e., the number of additional medically indicated labour inductions/cesarean deliveries required to prevent one perinatal death). Data from the United States showed that between 1995–96 and 1999–2000 rates of labour induction/cesarean delivery increased by 45.1 per 1,000 and perinatal mortality decreased by 0.31 per 1,000 total births among singleton pregnancies at > = 28 weeks of gestation. The marginal number needed to treat was 145 (45.1/0.31), showing that 145 excess labour inductions/cesarean deliveries in 1999–2000 (relative to 1995–96) were responsible for preventing 1 perinatal death among singleton pregnancies at > = 28 weeks gestation.
The fetuses at risk approach, with its focus on incidence measures, provides a coherent view of perinatal phenomena. It also provides a theoretical justification for medically indicated early delivery and reconciles the contemporary divide between obstetric theory and obstetric practice.
PMCID: PMC1851971  PMID: 17391525
24.  Malaria Transmission and Fetal Growth 
British Medical Journal  1974;3(5928):433-436.
In view of the known relation between infection of the maternal circulation of the placenta with Plasmodium falciparum and impaired fetal growth a study was made of the effect on birth weights of a malaria eradication campaign in the British Solomon Islands. Mean birth weights rose substantially within months of starting antimalarial operations. The increases between 1969 and 1971 averaged 252 g in babies of primigravidae and 165 g in all babies. The proportion of babies with birth weights of less than 2,500 g fell by 8% overall and by 20% among babies of primigravidae. The adverse effect of malaria transmission on fetal growth was apparently reversible if transmission of infection in the community was interrupted up to as late as the third trimester of pregnancy. The beneficial effects of malaria eradication operations on infant survival, child development, and social attitudes in developing countries are discussed.
PMCID: PMC1611476  PMID: 4606777
25.  Actuarial survival of a large Canadian cohort of preterm infants 
BMC Pediatrics  2005;5:40.
The increased survival of preterm and very low birth weight infants in recent years has been well documented but continued surveillance is required in order to monitor the effects of new therapeutic interventions. Gestation and birth weight specific survival rates most accurately reflect the outcome of perinatal care. Our aims were to determine survival to discharge for a large Canadian cohort of preterm infants admitted to the neonatal intensive care unit (NICU), and to examine the effect of gender on survival and the effect of increasing postnatal age on predicted survival.
Outcomes for all 19,507 infants admitted to 17 NICUs throughout Canada between January 1996 and October 1997 were collected prospectively. Babies with congenital anomalies were excluded from the study population. Gestation and birth weight specific survival for all infants with birth weight <1,500 g (n = 3419) or gestation ≤30 weeks (n = 3119) were recorded. Actuarial survival curves were constructed to show changes in expected survival with increasing postnatal age.
Survival to discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at 30 weeks. In infants with birth weights 600–699, survival to discharge was 62%, compared to 79% at 700–799 g and 96% at 1,000–1,099 g. In infants born at 24 weeks gestational age, survival was higher in females but there were no significant gender differences above 24 weeks gestation. Actuarial analysis showed that risk of death was highest in the first 5 days. For infants born at 24 weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks were 88 (CI 84,92)%, 70 (CI 64, 76)% and 60 (CI 53,66)% respectively. For smaller birth weights, female survival probabilities were higher than males for the first 40 days of life.
Actuarial analysis provides useful information when counseling parents and highlights the importance of frequently revising the prediction for long term survival particularly after the first few days of life.
PMCID: PMC1315360  PMID: 16280080

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