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1.  Small for Gestational Age and Higher Birth Weight Predict Childhood Obesity in Preterm Infants 
American journal of perinatology  2010;27(9):721-730.
We sought to determine the association between small for gestational age (SGA), birth weight, and childhood obesity within preterm polysubstance exposed children. We sampled 312 preterm children with 11-year body mass index (BMI; age- and sex-specific) data from the Maternal Lifestyle Study (51% girls, 21.5% SGA, 46% prenatal cocaine, and 55% tobacco exposed). Multinomial regression analyzed the association between 11-year obesity (OBE) and overweight (OW) and SGA, birth weight, first-year growth velocity, diet, and physical activity variables. Overall, 24% were OBE (BMI for age ≥95th percentile) and 16.7% were OW (BMI ≥85th and <95th percentiles). In adjusted analyses, SGA was associated with OW (odds ratio [OR]=3.4, confidence interval [CI] 1.5 to 7.5). Higher birth weight was associated with OBE (OR = 1.8, CI 1.3 to 2.4) and OW (OR=1.4, CI 1.1 to 2.0). Growth velocity was associated with OBE (OR=2.7, CI 1.8 to 4.0) and OW (OR=1.6, CI 1.1 to 2.4). Low exercise was associated with OBE (OR=2.1, CI 1.0 to 4.4) and OW (OR=2.1, CI 1.0 to 4.5). There was no effect of substance exposure on obesity outcomes. Many (41%) of these high-risk preterm 11-year-olds were obese/overweight. Multiple growth-related processes may be involved in obesity risk for preterm children, including fetal programming as indicated by the SGA effect.
PMCID: PMC2949419  PMID: 20408111
Childhood obesity; premature birth; infant SGA; birth weight; exercise; prenatal drug exposure
2.  Maternal HIV infection associated with small-for-gestational age infants but not preterm births: evidence from rural South Africa 
Human Reproduction (Oxford, England)  2012;27(6):1846-1856.
 Human immunodeficiency virus (HIV) is prevalent in many countries where small-for-gestational age (SGA) and premature delivery are also common. However, the associations between maternal HIV, preterm delivery and SGA infants remain unclear. We estimate the prevalence of SGA and preterm (<37 weeks) births, their associations with antenatal maternal HIV infection and their contribution to infant mortality, in a high HIV prevalent, rural area in South Africa.
Data were collected, in a non-randomized intervention cohort study, on all women attending antenatal clinics (2001–2004), before the availability of antiretroviral treatment. Newborns were weighed and gestational age was determined (based on last menstrual period plus midwife assessment antenatally). Poisson regression with robust variance assessed risk factors for preterm and SGA birth, while Cox regression assessed infant mortality and associated factors.
Of 2368 live born singletons, 16.6% were SGA and 21.4% were preterm. HIV-infected women (n= 1189) more commonly had SGA infants than uninfected women (18.1 versus 15.1%; P = 0.051), but percentages preterm were similar (21.8 versus 20.9%; P = 0.621). After adjustment for water source, delivery place, parity and maternal height, the SGA risk in HIV-infected women was higher [adjusted relative risk (aRR) 1.28, 95% confidence interval (CI): 1.06–1.53], but the association between maternal HIV infection and preterm delivery remained weak and not significant (aRR: 1.07, 95% CI: 0.91–1.26). In multivariable analyses, mortality under 1 year of age was significantly higher in SGA and severely SGA than in appropriate-for-gestational-age infants [adjusted hazard ratio (aHR): 2.12, 95% CI: 1.18–3.81 and 2.77, 95% CI: 1.56–4.91], but no difference in infant mortality was observed between the preterm and term infants (aHR: 1.18 95% CI: 0.79–1.79 for 34–36 weeks and 1.31, 95% CI: 0.58–2.94 for <34 weeks).
Maternal HIV infection increases the risk of SGA, but not preterm births, in this cohort.
PMCID: PMC3357196  PMID: 22442245
HIV; SGA; preterm; Africa; low birthweight
3.  Labour and Neonatal Outcome in Small for Gestational Age Babies Delivered Beyond 36+0 Weeks: A Retrospective Cohort Study 
Journal of Pregnancy  2010;2011:293516.
Objective. Small for gestational age (SGA) is associated with increased neonatal morbidity and mortality. At present, evidence on whether these pregnancies should be managed expectantly or by induction is lacking. To get insight in current policy we analysed data of the National Dutch Perinatal Registry (PRN). Methods. We used data of all nulliparae between 2000 and 2005 with a singleton in cephalic presentation beyond 36+0 weeks, with a birth weight below the 10th percentile. We analysed two groups of pregnancies: (I) with isolated SGA and (II) with both SGA and hypertensive disorders. Onset of labour was related to route of delivery and neonatal outcome. Results. Induction was associated with a higher risk of emergency caesarean section (CS), without improvement in neonatal outcome. For women with isolated SGA the relative risk of emergency CS after induction was 2.3 (95% Confidence Interval [CI] 2.1 to 2.5) and for women with both SGA and hypertensive disorders the relative risk was 2.7 (95% CI 2.3 to 3.1). Conclusion. Induction in pregnancies complicated by SGA at term is associated with a higher risk of instrumental deliveries without improvement of neonatal outcome. Prospective studies are needed to determine the best strategy in suspected IUGR at term.
PMCID: PMC3066629  PMID: 21490789
4.  Prepregnancy body mass index, smoking during pregnancy, and infant birth weight 
Annals of epidemiology  2011;21(6):413-420.
Smoking during pregnancy is strongly associated with increased risk of small for gestational age (SGA) and low birth weight, while elevated prepregnancy body mass index (BMI) is associated with a decreased risk of SGA and higher birth weight. We investigated the combined effect of prenatal smoking and prepregnancy BMI on risk of SGA and on birth weight.
A total of 34,928 singleton, term pregnancies in residents of New York City between 1995 and 2003 were evaluated in multivariable regression models of birth weight and risk of SGA.
Increasing prepregnancy BMI reduced the risk of SGA and increased birth weight. The effect of prenatal smoking on birth weight and SGA diminished in women as their prepregnancy BMI increased, such that prenatal smoking did not significantly impact the risk of SGA among women who were overweight or obese prior to pregnancy. Prenatal smoking decreased mean birth weight by 187 grams (95% confidence interval (CI): -337, -37) among underweight women, by 129 grams (95% CI: -170, -87) among normal weight women, by 46 grams (95% CI: -113, +20) among overweight women, and by 75 grams (95% CI: -162, +11) among obese women.
This study suggests that the effect of smoking during pregnancy on SGA and birth weight is present in underweight and normal weight women but markedly reduced among obese and overweight women.
PMCID: PMC3090467  PMID: 21421328
birth weight; body mass index; cigarette smoking; fetal growth retardation; infant; small for gestational age
5.  Prevalence of Small-for-Gestational-Age and Its Mortality Risk Varies by Choice of Birth-Weight-for-Gestation Reference Population 
PLoS ONE  2014;9(3):e92074.
We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations.
We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality.
The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in India, depending on the reference population. Females had higher rates of SGA than males using reference populations that were not sex specific. SGA prevalence was lowest when using reference populations from low-income countries. Infants who were both preterm and SGA had much higher mortality risk than those who were term and appropriate-for-gestational-age. Risk ratios for those who are both preterm and SGA ranged from 7.34–17.98 in Nepal and 5.29–11.98 in India, depending on the reference population.
These results demonstrate the value of a common birth-weight-for-gestation reference population that will facilitate comparisons of SGA prevalence and mortality risk across research studies.
PMCID: PMC3958448  PMID: 24642757
6.  Correlates and outcomes of preterm birth, low birth weight, and small for gestational age in HIV-exposed uninfected infants 
Preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) contribute to neonatal mortality. Maternal HIV-1 infection has been associated with an increased risk of PTB, but mechanisms underlying this association are undefined. We describe correlates and outcomes of PTB, LBW, and SGA in HIV-exposed uninfected infants.
This was a retrospective analysis of cohort study. Between 1999–2002, pregnant, HIV-infected women were enrolled into an HIV-1 transmission study. Logistic regression was used to identify correlates of PTB, LBW and SGA in HIV-negative, spontaneous singleton deliveries. Associations between birth outcomes and mortality were measured using survival analyses.
In multivariable models, maternal plasma (OR = 2.1, 95% CI = 1.1-3.8) and cervical HIV-1 RNA levels (OR = 1.6, 95% CI = 1.1-2.4), and CD4 < 15% (OR = 2.4, 95% CI = 1.0-5.6) were associated with increased odds of PTB. Abnormal vaginal discharge and cervical polymorphonuclear leukocytes were also associated with PTB. Cervical HIV-1 RNA level (OR = 2.4, 95% CI = 1.5-6.7) was associated with an increased odds of LBW, while increasing parity (OR = 0.46, 95% CI = 0.24-0.88) was associated with reduced odds. Higher maternal body mass index (OR = 0.75, 95% CI = 0.61-0.92) was associated with a reduced odds of SGA, while bacterial vaginosis was associated with >3-fold increased odds (OR = 3.2, 95% CI = 1.4-7.4). PTB, LBW, and SGA were each associated with a >6-fold increased risk of neonatal death, and a >2-fold increased rate of infant mortality within the first year.
Maternal plasma and cervical HIV-1 RNA load, and genital infections may be important risk factors for PTB in HIV-exposed uninfected infants. PTB, LBW, and SGA are associated with increased neonatal and infant mortality in HIV-exposed uninfected infants.
PMCID: PMC3897882  PMID: 24397463
Preterm birth; Low birth weight; Small for gestational age; Pediatric HIV
7.  Outcomes of small for gestational age micropremies depending on how young or how small they are 
Korean Journal of Pediatrics  2011;54(6):246-252.
The outcomes of small for gestational age (SGA) infants especially in extremely low birth weight infants (ELBWIs) are controversial. This study evaluated the mortality and morbidity of ELBWIs, focusing on whether or not they were also SGA.
The medical records of 415 ELBWIs (birth weight <1,000 g), who were inborn and admitted to the Samsung Medical Center neonatal intensive care unit from January 2000 to December 2008, were reviewed retrospectively. Mortality and morbidities were compared by body size groups: very SGA (VSGA), birth weight ≤3rd percentile; SGA, 3rd to 10th percentile; and appropriate for gestational age (AGA) infants, >10th percentile for gestational age. For gestational subgroup analysis, groups were divided into infants with gestational age ≤24+6 weeks (subgroup I), 25+0 to 26+6 weeks (subgroup II), and ≥27+0 weeks (subgroup III).
Gestational age was 29+2±2+6 weeks in the VSGA infants (n=49), 27+5±2+2 weeks in the SGA infants (n=45), and 25+4±1+4 weeks in AGA infants (n=321). Birth weight was 692±186.6 g, 768±132.9 g, and 780±142.5 g in the VSGA, SGA, and AGA groups, respectively. Cesarean section rate and maternal pregnancy-induced hypertension were more common in the VSGA and SGA than in AGA pregnancies. However, chorioamnionitis was more common in the AGA group. The mortalities of the lowest gestational group (subgroup I), and also of the lower gestational group (subgroup I+II) were significantly higher in the VSGA group than the SGA or AGA groups (P=0.020 and P=0.012, respectively). VSGA and SGA infants showed lower incidence in respiratory distress syndrome, ductal ligation, bronchopulmonary dysplasia, intraventricular hemorrhage than AGA group did. However, by multiple logistic regression analysis of each gestational subgroup, the differences were not significant.
Of ELBWIs, extremely SGA in the lower gestational subgroups, had an impact on mortality, which may provide information useful for prenatal counseling.
PMCID: PMC3174360  PMID: 21949519
Small for gestational age; Extremely low birth weight infants; Mortality; Morbidity
8.  Does Lack of Multinutrient Supplementation During Early Pregnancy Increase Vulnerability to Alcohol-Related Preterm or Small-for-Gestational-Age Births? 
Maternal and Child Health Journal  2010;15(8):1324-1332.
The objective of this study was to assess whether women who do not take multinutrient supplements during early pregnancy are more susceptible to the effects of low-to-moderate alcohol consumption on preterm birth and small-for-gestational-age birth (SGA) compared to women who do take multinutrients. This analysis included 800 singleton live births to mothers from a cohort of pregnant women recruited for a population-based cohort study conducted in the Kaiser Permanente Medical Care Program in Northern California. Participants were recruited in their first trimester of pregnancy and information about their alcohol use and supplement intake during pregnancy was collected. Preterm birth (n = 53, 7%) was defined as a delivery prior to 37 completed weeks of gestation and SGA birth (n = 124, 16%) was defined as birth weight less than the 10th percentile for the infant’s gestational age and sex compared to US singleton live births. A twofold increase in the odds of SGA birth attributed to low-to-moderate alcohol intake was found among multinutrient supplement non-users (95% CI: 1.1, 5.3). Yet, among multinutrient supplement users, there was no increased risk of an SGA birth for women who drank low-to-moderately compared to women who abstained (aOR: 0.97, 95% CI: 0.6, 1.6). Similar results emerged for preterm birth. Our findings provide marginal evidence that multinutrient supplementation during early pregnancy may modify the risk of SGA births and preterm birth associated with alcohol consumption during pregnancy and may have important implications for pregnant women and women of child-bearing age. However, future research needs to be conducted.
PMCID: PMC3195813  PMID: 20949322
Low-to-moderate alcohol use; Multinutrient supplement use; Preterm birth; SGA birth; Multivitamin use
9.  Clinical Prediction in Early Pregnancy of Infants Small for Gestational Age by Customised Birthweight Centiles: Findings from a Healthy Nulliparous Cohort 
PLoS ONE  2013;8(8):e70917.
Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants.
5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15±1 weeks’ gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20±1 weeks’. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated.
633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15±1 weeks’ included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥80. Recreational walking ≥4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10th centile and increasing uterine artery Doppler resistance at 20±1 weeks’ were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively.
Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension.
PMCID: PMC3733741  PMID: 23940665
10.  CXCL10/IP-10 
Interferon (IFN)-γ inducible protein, CXCL10/IP-10, is a member of the CXC chemokine family with pro-inflammatory and anti-angiogenic properties. This chemokine has been proposed to be a key link between inflammation and angiogenesis. The aim of this study was to determine whether preeclampsia and delivery of a small for gestational age (SGA) neonate are associated with changes in maternal serum concentration of CXCL10/IP-10.
This cross-sectional study included patients in the following groups: (1) non pregnant women (N=49); (2) women with normal pregnancies (N=89); (3) patients with preeclampsia (N=100); and (4) patients who delivered an SGA neonate (N=78). SGA was defined as birth weight below the 10th percentile. Maternal serum concentrations of CXCL10/IP-10 were measured by sensitive immunoassay. Non-parametric statistics were used for analysis.
(1) Patients with normal pregnancies had a significantly higher median serum concentration of CXCL10/IP-10 than non-pregnant women (median: 116.1 pg/mL, range: 40.7-1314.3 vs. median: 90.3 pg/mL, range: 49.2-214.7, respectively; p=0.002); (2) no significant correlation was found between maternal serum concentration of CXCL10/IP-10 and gestational age (between 19 and 38 weeks); (3) there were no differences in median serum CXCL10/IP-10 concentrations between patients who delivered an SGA neonate and those with normal pregnancies (median: 122.4 pg/mL, range: 37.3-693.5 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p>0.05); (4) patients with preeclampsia had a higher median serum concentration of CXCL10/IP-10 than normal pregnant women (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p<0.05); (5) patients with preeclampsia had a higher median concentration of CXCL10/IP-10 than those who delivered an SGA neonate (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 122.4 pg/mL, range: 37.3-693.5, respectively; p<0.05).
Patients with preeclampsia have significantly higher serum concentrations of CXCL10/IP-10 than both normal pregnant women and mothers who have SGA neonates. These results are likely to reflect an anti-angiogenic state as well as an enhanced systemic inflammatory response in patients with preeclampsia. Alternatively, since preeclampsia and SGA share several mechanisms of disease, it is possible that a higher concentration of this chemokine may contribute to the clinical presentation of preeclampsia in patients with a similar intrauterine insult.
PMCID: PMC2396489  PMID: 17943641
Pregnancy; CXCL10; IP-10; chemokine; chemotactic cytokine; small for gestational age; SGA; angiogenesis
11.  Prenatal Cocaine Exposure and Small-for-Gestational-Age Status: Effects on Growth at 6 Years of age 
Neurotoxicology and teratology  2011;33(5):575-581.
To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.
Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.
At birth cocaine-exposed infants (n=364) had significantly lower growth parameters compared to non-exposed children (n=771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).
Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.
PMCID: PMC3183411  PMID: 21849244
Prenatal cocaine exposure; small for gestational age; childhood growth
12.  Correction of Systematic Bias in Ultrasound Dating in Studies of Small-for-Gestational-Age Birth: An Example From the Iowa Health in Pregnancy Study 
American Journal of Epidemiology  2012;176(5):443-455.
The authors examined whether early ultrasound dating (≤20 weeks) of gestational age (GA) in small-for-gestational-age (SGA) fetuses may underestimate gestational duration and therefore the incidence of SGA birth. Within a population-based case-control study (May 2002–June 2005) of Iowa SGA births and preterm deliveries identified from birth records (n = 2,709), the authors illustrate a novel methodological approach with which to assess and correct for systematic underestimation of GA by early ultrasound in women with suspected SGA fetuses. After restricting the analysis to subjects with first-trimester prenatal care, a nonmissing date of the last menstrual period (LMP), and early ultrasound (n = 1,135), SGA subjects’ ultrasound GA was 5.5 days less than their LMP GA, on average. Multivariable linear regression was conducted to determine the extent to which ultrasound GA predicted LMP dating and to correct for systematic misclassification that results after applying standard guidelines to adjudicate differences in these measures. In the unadjusted model, SGA subjects required a correction of +1.5 weeks to the ultrasound estimate. With adjustment for maternal age, smoking, and first-trimester vaginal bleeding, standard guidelines for adjudicating differences in ultrasound and LMP dating underestimated SGA birth by 12.9% and overestimated preterm delivery by 8.7%. This methodological approach can be applied by researchers using different study populations in similar research contexts.
PMCID: PMC3499119  PMID: 22886591
bias (epidemiology); gestational age; infant, small for gestational age; pregnancy; premature birth; ultra-sonography
13.  Preterm birth and reduced birthweight in first and second teenage pregnancies: a register-based cohort study 
Higher risks of preterm birth and small for gestational age babies have been reported in teenagers. The aim of this study was to investigate the relationship between first and second teenage pregnancies and preterm birth, birthweight and small for gestational age (SGA).
All women aged 14 to 29 yrs who gave birth to live singletons in the North Western Region of England between January 1st 2004 and December 31st 2006 were identified. Women were classified in three groups; 14-17 yrs, 18-19 yrs and 20-29 yrs (reference group). The outcome measures were preterm birth, very preterm birth, birthweight, SGA (< 5th percentile), very SGA (VSGA< 3rd percentile). We compared these outcome measures in teenagers' first and second pregnancies with those of mothers aged 20 to 29 yrs.
The risk of preterm birth was increased in first (OR = 1.21, [95% CI: 1.01-1.45]) and second (OR = 1.93, [95% CI: 1.38-2.69]) time mothers aged 14-17 yrs compared to the reference group. Birthweight was reduced in the first (mean difference = -24 g; [95% CI: -40, -7]) and second (mean difference = -80 g; [95% CI: -115, -46]) time mothers aged 14-17 yrs compared to the reference group. There was some evidence of a protective effect against VSGA in 14-17 yr old first time mothers (OR = 0.79, [95% CI: 0.63-0.99]).
Teenage mothers are at increased risk of preterm birth compared to adult mothers and this risk is further increased in second time teen pregnancies. This study highlights the importance of ensuring pregnant teenagers have appropriate antenatal care. A first pregnancy may be the first and only time a pregnant teenager interacts with health services and this opportunity for health education and the promotion of contraception should not be overlooked.
PMCID: PMC2909926  PMID: 20618921
14.  Parental occupation and risk of small-for-gestational-age births: a nationwide epidemiological study in Sweden 
Human Reproduction (Oxford, England)  2010;25(4):1044-1050.
Although evidence suggests that some occupations may be a risk factor for small-for-gestational age (SGA) birth, associations between a wide range of maternal and paternal occupations and risk of SGA births remain unclear. Our objective was to analyze the risk of SGA births by parental occupation, including the entire Swedish population of mothers (≥20 years) and fathers.
We linked nationwide data (1990–2004) on singletons born to employed mothers to nationwide data on maternal and paternal occupation and other individual-level variables. Information on parental occupations was obtained from the 1990 census. Approximately 95% of SGA births (calculated using normative data) were defined on the basis of ultrasound. Odds ratios of SGA birth were calculated with 95% confidence intervals. Women and men were analyzed separately.
There were 816 310 first singleton live births during the study period, of which 29 603 were SGA events. Families with low incomes had an increased risk of SGA births. After accounting for maternal age at the infant's birth, period of birth, family income, region of residence, marital status and smoking habits, several maternal occupational groups (including ‘mechanics and iron and metalware workers’ and ‘packers, loaders and warehouse workers’) had a significantly higher risk of SGA birth than the reference group (all women in the study population). Among paternal occupational groups, only waiters had an increased risk of SGA birth.
This large-scale follow-up study shows that maternal occupation affects risk of SGA birth, whereas paternal occupation does not seem to have an impact on SGA birth. Further studies are required to examine the specific agents in those maternal occupations that are associated with an increased risk of SGA birth.
PMCID: PMC2839909  PMID: 20133322
family income; follow-up study; occupational exposure; small for gestational age
15.  Combination Antiretroviral Use and Preterm Birth 
The Journal of Infectious Diseases  2012;207(4):612-621.
Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth.
Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics.
Results. Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens.
Conclusions. Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.
PMCID: PMC3549601  PMID: 23204173
preterm birth; antiretrovirals; pregnancy; small for gestational age
16.  Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana 
The Journal of Infectious Diseases  2012;206(11):1695-1705.
Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings.
Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count.
Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB.
Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB.
PMCID: PMC3488194  PMID: 23066160
17.  Does the individualized birthweight reference outperform a simple ultrasound reference in predicting long-term child neurodevelopment? 
Being small-for-gestational-age (SGA) is associated with an increased risk of morbidity, but questions remain about how best to diagnose SGA, and thus, predict poor health consequences. The authors sought to compare an individualized reference for defining SGA with a simple ultrasound reference in predicting poor cognitive development at age five.
The authors used data from the Successive SGA Births Study, a prospective study including 699 Alabaman and 618 Scandinavian women recruited from 1986 to 1988, and whose children had cognitive development scores measured at age five. Sensitivity, specificity and positive predictive value (PPV) were estimated for each reference using cognitive development as the benchmark. Relative risk of poor neurodevelopment was calculated, comparing infants classified as SGA by either reference with infants not classified as SGA.
The individualized reference had higher sensitivity and PPV in predicting poor neurodevelopment. Babies defined as SGA by the individualized reference alone had a higher risk (RR=2.20, 95% CI: 1.20, 4.00) of poor cognitive outcome, while those identified by the ultrasound reference alone did not (RR=0.95, 95% CI: 0.45, 2.01). None of the references could predict poor neurodevelopment well at age five.
The individualized birthweight reference modestly outperforms the simple ultrasound reference in identifying SGA infants with poor child neurodevelopment. However, neither reference can predict child neurodevelopment well.
PMCID: PMC3059357  PMID: 21154763
Birth Weight; Fetal Development; Infant; Small for Gestational Age; Wechsler Scales
18.  TCF7L2 rs7903146 variant does not associate with smallness for gestational age in the French population 
BMC Medical Genetics  2007;8:37.
In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes (T2D), has been also associated with a lower body mass index (BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance.
The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age (SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight (AGA). Two groups of French Caucasian subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 764), and AGA (25th < birth weight < 75th percentile; n = 627). Family-based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees.
The rs7903146 genotypic distributions between AGA (30.7%) and SGA (29.0%) were not statistically different (allelic OR = 0.92 [0.78–1.09], p = 0.34). Family association-based studies did not show a distortion of T allele transmission in SGA subjects (p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion (p = 0.03) and a higher fasting glycaemia (p = 0.002) were detected in carriers of the T allele.
The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.
PMCID: PMC1920504  PMID: 17593304
19.  Prenatal Application of the Individualized Fetal Growth Reference 
American Journal of Epidemiology  2011;173(5):539-543.
The individualized reference for defining small for gestational age (SGA) at birth has gained popularity in recent years. However, its utility on fetal assessment has not been evaluated. The authors compare an individualized with an ultrasound reference in predicting poor perinatal outcomes. Data from a large clinical trial in predominantly white US women (1987–1991) with singleton pregnancies (n = 9,526) were used. The individualized reference classified fewer SGA fetuses than the ultrasound reference, but the risks of adverse outcomes were similar between fetuses classified by both references. The risk increased substantially only when the percentiles fell below the 5th percentile (likelihood ratio positive at birth = 2.68 (95% confidence interval (CI): 2.00, 3.58) and 3.13 (95% CI: 2.34, 4.18) for ultrasound and individualized references, respectively). SGA fetuses defined by either the individualized or ultrasound reference alone had risk ratios of adverse outcomes of 1.91 (95% CI: 0.77, 4.77) and 1.18 (95% CI: 0.37, 3.77), respectively, compared with normal fetuses (the difference between these 2 risk ratios, P = 0.71). The authors conclude that neither the ultrasound-based nor the individualized reference does well in predicting adverse perinatal outcomes. The 5th percentile may be a better cutpoint than the 10th percentile in defining SGA.
PMCID: PMC3044839  PMID: 21252054
fetal growth retardation; infant, small for gestational age; perinatal mortality
20.  Birth Status, Child Growth, and Adult Outcomes in Low- and Middle-Income Countries☆ 
The Journal of Pediatrics  2013;163(6):1740-1746.e4.
To assess the impact of being born preterm or small for gestational age (SGA) on several adult outcomes.
Study design
We analyzed data for 4518 adult participants in 5 birth cohorts from Brazil, Guatemala, India, the Philippines, and South Africa.
In the study population, 12.8% of males and 11.9% of females were born preterm, and 26.8% of males and 22.4% of females were born term but SGA. Adults born preterm were 1.11 cm shorter (95% CI, 0.57-1.65 cm), and those born term but SGA were 2.35 cm shorter (95% CI, 1.93-2.77 cm) compared with those born at term and appropriate size for gestational age. Blood pressure and blood glucose level did not differ by birth category. Compared with those born term and at appropriate size for gestational age, schooling attainment was 0.44 years lower (95% CI, 0.17-0.71 years) in those born preterm and 0.41 years lower (95% CI, 0.20-0.62 years) in those born term but SGA.
Being born preterm or term but SGA is associated with persistent deficits in adult height and schooling, but is not related to blood pressure or blood glucose level in low- and middle-income settings. Increased postnatal growth is associated with gains in height and schooling regardless of birth status, but not with increases in blood pressure or blood glucose level.
PMCID: PMC3849851  PMID: 24064150
AGA, Appropriate for gestational age; BMI, Body mass index; GA, Gestational age; IFG, Impaired fasting glucose; LGA, Large for gestational age; LMP, Last menstrual period; SGA, Small for gestational age
21.  Inadequate prenatal care and its association with adverse pregnancy outcomes: A comparison of indices 
The objectives of this study were to determine rates of prenatal care utilization in Winnipeg, Manitoba, Canada from 1991 to 2000; to compare two indices of prenatal care utilization in identifying the proportion of the population receiving inadequate prenatal care; to determine the association between inadequate prenatal care and adverse pregnancy outcomes (preterm birth, low birth weight [LBW], and small-for-gestational age [SGA]), using each of the indices; and, to assess whether or not, and to what extent, gestational age modifies this association.
We conducted a population-based study of women having a hospital-based singleton live birth from 1991 to 2000 (N = 80,989). Data sources consisted of a linked mother-baby database and a physician claims file maintained by Manitoba Health. Rates of inadequate prenatal care were calculated using two indices, the R-GINDEX and the APNCU. Logistic regression analysis was used to determine the association between inadequate prenatal care and adverse pregnancy outcomes. Stratified analysis was then used to determine whether the association between inadequate prenatal care and LBW or SGA differed by gestational age.
Rates of inadequate/no prenatal care ranged from 8.3% using APNCU to 8.9% using R-GINDEX. The association between inadequate prenatal care and preterm birth and LBW varied depending on the index used, with adjusted odds ratios (AOR) ranging from 1.0 to 1.3. In contrast, both indices revealed the same strength of association of inadequate prenatal care with SGA (AOR 1.4). Both indices demonstrated heterogeneity (non-uniformity) across gestational age strata, indicating the presence of effect modification by gestational age.
Selection of a prenatal care utilization index requires careful consideration of its methodological underpinnings and limitations. The two indices compared in this study revealed different patterns of utilization of prenatal care, and should not be used interchangeably. Use of these indices to study the association between utilization of prenatal care and pregnancy outcomes affected by the duration of pregnancy should be approached cautiously.
PMCID: PMC2386440  PMID: 18452623
22.  Birth Outcomes Across Three Rural-Urban Typologies in the Finger Lakes Region of New York 
The study is a descriptive, population-based analysis of birth outcomes in the New York State Finger Lakes region designed to determine whether perinatal outcomes differed across 3 rural typologies.
Hospital birth data for the Finger Lakes region from 2006-2007 were used to identify births classified as low birthweight (LBW), small for gestational age (SGA), and preterm delivery (PTD). Maternal residences were defined using 3 existing zip-code-level rural-urban typologies: Census Bureau zip codes, Rural-Urban Commuting Area codes, and Primary Service Areas. Within each typology, rural maternal characteristics and birth outcomes were compared to those in urban areas using multivariable logistic regression models.
In bivariate analyses, rurality was associated with LBW and SGA for all typologies, while PTD was associated with residence in the Census Bureau typology only. After controlling for demographic characteristics, births to mothers in the most rural level of the Census Bureau typology and to all rural mothers in the RUCA and Primary Service Area typologies were more likely to be LBW and PTD. SGA was not consistently associated with residence across typologies.
The typologies produced similar results for these outcomes, although effects were of greater magnitude in the RUCA and Primary Service Area typologies than in the Census Bureau typology. Comparison across typologies can have practical implications for researchers and policy makers interested in understanding the dynamics of rurality and birth outcomes in their regions.
PMCID: PMC3337719  PMID: 22458317
birth outcomes; regression analysis; residence characteristics; rural
23.  The relationship between maternal body mass index and tobacco use on small for gestational age infants 
American journal of perinatology  2011;29(3):153-158.
To estimate the association between pre-pregnancy body mass index (BMI) and small for gestational age (SGA) neonates, and to determine if there is a synergistic effect of tobacco use on SGA across all BMI strata.
Study Design
Retrospective cohort study of 65,104 patients seen for second-trimester ultrasound. BMI was categorized into underweight, normal weight, overweight, and obese. SGA was defined as birth weight <10th percentile and <5th percentile. Univariable and multivariable logistic regression analyses were used to evaluate the association between BMI and SGA. Stratified analyses and tests for effect modification were performed to evaluate for a potential synergistic effect between tobacco use and abnormal pre-pregnancy BMI on SGA.
After controlling for potential confounders, underweight BMI was significantly associated with an increased risk for SGA <10th percentile (aOR 1.8, 95% CI 1.5–2.1) while overweight (aOR 0.7, 95% CI 0.7–0.8) and obese BMI (aOR 0.6, 95% CI 0.5–0.7) were associated with a decreased risk of SGA. There was no effect modification of tobacco use on the risk of SGA across all BMI categories.
While both tobacco and underweight BMI are independently associated with SGA, there was no evidence of synergism. Continued emphasis on both smoking cessation and maintenance of normal pre-pregnancy BMI remain paramount to decreasing the incidence of SGA.
PMCID: PMC3629943  PMID: 21786218
body mass index; tobacco; small for gestational age; underweight
24.  The risk of intrauterine fetal death in the small-for-gestational-age fetus 
We sought to evaluate the risk of intrauterine fetal death (IUFD) in small-for-gestational-age (SGA) fetuses.
We analyzed a retrospective cohort of all births in the United States in 2005, as recorded in a national database. We calculated the risk of IUFD within 3 sets of SGA threshold categories as well as within non-SGA pregnancies using the number of at-risk fetuses as the denominator.
The risk of IUFD increased with gestational age and was inversely proportional to percentile of birthweight for gestational age. The risk for IUFD in those <3rd percentile was as high as 58.0 IUFDs per 10,000 at-risk fetuses, 43.9 for <5th percentile, and 26.3 for <10th percentile compared to 5.1 for non-SGA gestations.
There is an increase in the risk of IUFD in SGA fetuses compared to non-SGA fetuses at all gestational ages with the greatest risk demonstrated in the lowest percentile cohort evaluated.
PMCID: PMC3724359  PMID: 23021697
birthweight; fetal death; small for gestational age; stillbirth
25.  Effects of gestation and birth weight on the growth and development of very low birthweight small for gestational age infants: a matched group comparison 
AIMS—To investigate the effects of small for gestational age (SGA) in very low birthweight (VLBW) infants on growth and development until the fifth year of life.
METHODS—VLBW (< 1500 g) infants, selected from a prospective study, were classified as SGA (n = 115) on the basis of birth weight below the 10th percentile for gestational age and were compared with two groups of appropriate for gestational age (AGA) infants matched according to birth weight (AGA-BW; n = 115) or gestation at birth (AGA-GA; n = 115). Prenatal, perinatal, and postnatal risk factors were recorded, and duration and intensity of treatment were computed from daily assessments. Body weight, length, and head circumference were measured at birth, five and 20 months (corrected for prematurity), and at 56 months. General development was assessed at five and 20 months with the Griffiths scale of babies abilities, and cognitive development at 56 months with the Columbia mental maturity scales, a vocabulary (AWST) and language comprehension test (LSVTA).
RESULTS—Significant group differences were found in complications (pregnancy, birth, and neonatal), parity, and multiple birth rate. The AGA-GA group showed most satisfactory growth up to 56 months, with both the AGA-BW and SGA groups lagging behind. The AGA-GA group also scored significantly more highly on all developmental and cognitive tests than the other groups. Developmental test results were similar for the SGA and AGA-BW groups at five and 20 months, but AGA-BW infants (lowest gestation) had lower scores on performance intelligence quotient and language comprehension at 56 months than the SGA group. When prenatal and neonatal complications, parity, and multiple birth were accounted for, group differences in growth remained, but differences in cognitive outcome disappeared after five months.
CONCLUSIONS—Being underweight and with a short gestation (SGA and VLBW) leads to poor weight gain and head growth in infancy but does not result in poorer growth than in infants of the same birth weight but shorter gestation (AGA-BW) in the long term. SGA is related to early developmental delay and later language problems; however, neonatal complications may have a larger detrimental effect on long term cognitive development of VLBW infants than whether they are born SGA or AGA.

PMCID: PMC1721075  PMID: 10794788

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