non-SGA Controls Research Articles

Self-reported mental health difficulties were of limited use when screening for psychiatric diagnoses in adults born small for gestational age at term.

Being born small for gestational age (SGA) at term increases the risk of adverse health outcomes. We examined whether self-reported mental health differed between adults born SGA and non-SGA at term and could be used to screen for psychiatric diagnoses. We used the Strengths and Difficulties Questionnaire to gather data from 68 participants born SGA and 88 non-SGA controls at a mean age of 26.5 years. Group differences were analysed by linear regression. We calculated the area under the curve and the sensitivity, specificity and predictive values for psychiatric diagnoses. The mean total difficulties score was 1.9 (95% confidence interval 0.4-3.5) points higher for participants born SGA. They also reported more internalising and emotional problems (p < 0.05). The areas under the curve were 0.82 and 0.68 in the SGA and control groups, respectively. Among participants born SGA, the 90th percentile cut-off had a sensitivity of 0.38, a specificity of 0.93 and positive and negative predictive values of 0.75 and 0.71. The 80th percentile cut-off had higher sensitivity and lower specificity. Adults born SGA reported more mental health difficulties than non-SGA controls. The low sensitivity using the 90th percentile cut-off suggests that a lower cut-off should be considered.

Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Early Pregnancy and Small for Gestational Age in Southern Sweden.

Small for gestational age (SGA) is considered an adverse birth outcome. Per- and polyfluoralkyl substances (PFAS) have become increasingly investigated as contributing environmental factors, thus far with inconclusive results. The current study aimed to investigate the hypothesized association between increased maternal PFAS levels in early pregnancy and an increased risk for SGA birth. This population-based study used data from a sample of children born in Scania, Southern Sweden, between 1995 and 2009. Two groups were compared: cases born with SGA (n = 298) and non-SGA controls (n = 580). The cases consisted of two subgroups: one included women whose children's growth in late pregnancy was in the lowest quartile, and another included women from the remaining growth quartiles. Corresponding maternal serum samples were collected from a biobank and analyzed for concentrations of four types of PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The results were combined with information from birth registers and analyzed using Mann-Whitney U-tests and logistic regression-unadjusted as well as adjusted for potential confounders. In conclusion, elevated maternal concentrations of PFAS were not associated with an increased risk of SGA birth. However, significant ORs were observed in a subgroup analysis restricted to women of Nordic origin (unadjusted OR 3.2 and adjusted OR 2.4) for PFHxS.

Health-related quality of life in young adults born small for gestational age: a prospective cohort study

BackgroundIndividuals born small for gestational age (SGA) have an increased risk of several adverse health outcomes, but their health-related quality of life (HRQoL) across young adulthood has yet to be studied. The main aim of this study was to investigate if being born SGA at term is associated with poor HRQoL at 32 years of age. A second aim was to explore longitudinal changes in HRQoL from age 20 to 32 years.MethodsIn the prospective NTNU Low Birth Weight in a Lifetime Perspective study, 56 participants born SGA and 68 non-SGA control participants completed the Short Form 36 Health Survey (SF-36) at age 32 years to assess HRQoL. The SF-36 was also administrated at age 20 and 28 years. Longitudinal changes in the eight SF-36 domains and the two component summaries from 20 to 32 years were analyzed by linear mixed models. In total, 82 adults born SGA and 98 controls participated at least once and were included in the longitudinal analyses.ResultsAt age 32 years the participants born SGA scored 14.8 (95% CI 4.7 to 25.3) points lower in the SF-36 role-physical domain compared with the control group, i.e. more problems with work or other daily activities due to physical health problems. The longitudinal analyses showed significant group differences from 20 to 32 years in the role-emotional domain, and in the physical and mental component summaries. Among participants born SGA, the physical component summary decreased from age 20 to 28 years (-3.2, 95% CI -5.0 to -1.8), while the mental component summary (6.0, 95% CI 2.9 to 8.6) and role-emotional domain score (19.3, 95% CI 9.9 to 30.3) increased, but there were no further changes from 28 to 32 years. There were no longitudinal changes in the control group from 20 to 32 years.ConclusionOverall, individuals born SGA at term reported similar HRQoL at age 32 years compared with non-SGA controls. Self-perceived mental health improved during young adulthood among individuals born SGA, while self-perceived physical health deteriorated. The latter findings warrant further investigation.

Genomic imbalances in the placenta are associated with poor fetal growth

BackgroundFetal growth restriction (FGR) is associated with increased risks for complications before, during, and after birth, in addition to risk of disease through to adulthood. Although placental insufficiency, failure to supply the fetus with adequate nutrients, underlies most cases of FGR, its causes are diverse and not fully understood. One of the few diagnosable causes of placental insufficiency in ongoing pregnancies is the presence of large chromosomal imbalances such as trisomy confined to the placenta; however, the impact of smaller copy number variants (CNVs) has not yet been adequately addressed. In this study, we confirm the importance of placental aneuploidy, and assess the potential contribution of CNVs to fetal growth.MethodsWe used molecular-cytogenetic approaches to identify aneuploidy in placentas from 101 infants born small-for-gestational age (SGA), typically used as a surrogate for FGR, and from 173 non-SGA controls from uncomplicated pregnancies. We confirmed aneuploidies and assessed mosaicism by microsatellite genotyping. We then profiled CNVs using high-resolution microarrays in a subset of 53 SGA and 61 control euploid placentas, and compared the load, impact, gene enrichment and clinical relevance of CNVs between groups. Candidate CNVs were confirmed using quantitative PCR.ResultsAneuploidy was over tenfold more frequent in SGA-associated placentas compared to controls (11.9% vs. 1.1%; p = 0.0002, OR = 11.4, 95% CI 2.5–107.4), was confined to the placenta, and typically involved autosomes, whereas only sex chromosome abnormalities were observed in controls. We found no significant difference in CNV load or number of placental-expressed or imprinted genes in CNVs between SGA and controls, however, a rare and likely clinically-relevant germline CNV was identified in 5.7% of SGA cases. These CNVs involved candidate genes INHBB, HSD11B2, CTCF, and CSMD3.ConclusionsWe conclude that placental genomic imbalances at the cytogenetic and submicroscopic level may underlie up to ~ 18% of SGA cases in our population. This work contributes to the understanding of the underlying causes of placental insufficiency and FGR, which is important for counselling and prediction of long term outcomes for affected cases.

Brain Morphometry and Cognition in Young Adults Born Small for Gestational Age at Term

To examine brain volumes and cortical surface area and thickness and to relate these brain measures to cognitive function in young adults born small for gestational age (SGA) at term compared with non-SGA control patients. This population-based follow-up study at age 20 years included 58 term-born SGA (birth weight <10th percentile, mean: 2915 g) and 81 non-SGA controls (birth weight ≥ 10th percentile, mean: 3707 g). Brain volumes and cortical surface area and thickness were investigated with magnetic resonance imaging, which was successfully obtained in 47 SGA patients and 61 control patients. Cognitive function was assessed using the Wechsler Adult Intelligence Scale, 3rd edition. A subgroup analysis was performed in the SGA group among subjects diagnosed with fetal growth restriction (FGR) based on repeated fetal ultrasound measurements. The SGA group showed regional reductions in cortical surface area, particularly in the frontal, parietal, and temporal lobes. Total brain volume, cortical gray matter, cerebral white matter, and putamen volumes were reduced in the SGA group compared with control patients, but there were no differences in specific subcortical brain structure volumes when correcting for intracranial volume. Reductions were most pronounced among SGA subjects with FGR. No associations were found between brain measures and IQ measures in either group. Young adults born SGA at term show a global reduction in brain volume as well as regional reductions in cortical surface area. We speculate whether these reductions may be confined to those exposed to FGR. None of the brain measures correlated with cognition.

Neuropsychological Deficits in Young Adults Born Small-for-Gestational Age (SGA) at Term

Reduced IQ, learning difficulties and poor school performance have been reported in small-for-gestational-age (SGA) subjects. However, few studies include a comprehensive neuropsychological assessment. Our aim was to study neuropsychological functioning in young adults born SGA at term. A comprehensive neuropsychological test battery was administered to 58 SGA subjects (birth weight <10th centile) born at term, and 81 term non-SGA controls (birth weight ≥10th centile). The SGA group obtained significantly (p < .01) lower scores on the attention, executive and memory domains compared to non-SGA controls and showed higher risk of obtaining scores below -1.5 SD on the memory domain (odds ratio = 13.3, 95% confidence interval: 1.57, 112.47). At a subtest level, the SGA group obtained lower scores on most neuropsychological tests, with significant differences on 6 of 46 measures: the Trail Making Test 3 (letter sequencing), the Wechsler Memory Scale mental control and the auditory immediate memory scale, the Design Fluency, the Stroop 3 (inhibition) and the Visual Motor Integration (VMI) motor coordination subtest. Young adults born SGA score more poorly on neuropsychological tests compared with non-SGA controls. Differences were modest, with more significant differences in the memory domain.

A case–control study to examine the association between breastfeeding during late pregnancy and risk of a small‐for‐gestational‐age birth in Lima, Peru

Excessive demands on maternal nutritional status may be a risk factor for poor birth outcomes. This study examined the association between breastfeeding during late pregnancy (≥ 28 weeks) and the risk of having a small-for-gestational-age (SGA) newborn, using a matched case-control design (78 SGA cases: birthweight <10th percentile for gestational age; 150 non-SGA controls: 50th percentile <birthweight <90th percentile for gestational age). Between March 2006 and April 2007, project midwives visited daily three government hospitals in Lima, Peru and identified cases and matched controls based on hospital, gestational age, and inter-gestational period. Mothers were interviewed and clinical chart extractions were completed. Factors associated with risk of SGA were assessed by their adjusted odds ratios (aOR) from conditional logistic regression. Exposure to an overlap of breastfeeding during late pregnancy was not associated with an increased risk of having a SGA newborn [aOR=0.58, 95% confidence interval (CI): 0.10-3.30]. However, increased risk was associated with having a previous low-birthweight birth (aOR=6.53; 95% CI: 1.43-29.70) and a low intake of animal source foods (<25th percentile; aOR=2.26; 95% CI: 1.01-5.04), and tended to be associated with being short (<150 cm; aOR=2.05; 95% CI: 0.92-4.54). This study found no evidence to support the hypothesis that breastfeeding during late pregnancy increases the risk for SGA; however, studies with greater statistical power are needed to definitively examine this possible association and clarify whether there are other risks to the new baby, the toddler and the pregnant woman.

Maternal serum placental growth hormone at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates

Objective: To investigate whether the maternal serum concentration of human placental growth hormone (PGH) at 11–13 weeks’ gestation is altered in pregnancies that deliver small for gestational age (SGA) neonates. Methods: Maternal serum concentration of PGH was measured in 60 cases that subsequently delivered SGA neonates in the absence of preeclampsia and compared to 120 non-SGA controls. Results: In the SGA group, compared to the non-SGA group, there was no significant difference in the median PGH MoM (0.95 MoM, IQR 0.60–1.30 vs. 1.00 MoM, IQR 0.70–1.30, p = 0.97). There was no significant association between PGH MoM and birth weight percentile in either the SGA (p = 0.72) or in the non-SGA group (p = 0.63). Conclusion: Maternal serum PGH at 11–13 weeks’ gestation is unlikely to be a useful biochemical marker for early prediction of SGA.

Maternal serum insulin-like growth factor (IGF-I) and binding proteins IGFBP-1 and IGFBP-3 at 11–13 weeks’ gestation in pregnancies delivering small for gestational age neonates

To investigate the possible value of maternal serum concentration of insulin-like growth factor-I (IGF-I), IGF binding protein-1 (IGFBP-1) and IGFBP-3 at 11-13 weeks' gestation in the prediction of small-for-gestational age (SGA) neonates. Maternal serum concentrations of IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks were measured in 60 cases that subsequently delivered SGA neonates in the absence of pre-eclampsia, and compared to 120 non-SGA controls. In the SGA group, compared to the non-SGA group, there was significantly lower median IGF-I (61.8, IQR 43.4-93.4 ng/mL vs 94.9, IQR 56.7-131.2 ng/mL, p=0.002) and IGFBP-1 (58.2, IGR 39.8-84.9 ng/mL vs 81.4, IGR 57.3-105.5 ng/mL, p=0.002) but not IGFBP-3 (54.5, IGR 45.6-61.5 ng/mL vs 55.4, IGR 47.4-64.9 ng/mL, p=0.402). However, after multiple regression analysis and adjustment for maternal characteristics, these biomarkers were not useful in predicting SGA. Maternal serum IGF-I, IGFBP-1 and IGFBP-3 at 11-13 weeks are unlikely to be useful biochemical markers for early prediction of SGA.

Maternal Serum Adiponectin at 11–13 Weeks of Gestation in Pregnancies Delivering Small for Gestation Neonates

Objective: To investigate whether maternal serum levels of adiponectin in the first trimester are altered in pregnancies that subsequently deliver small for gestational age (SGA) neonates. Methods: Maternal serum adiponectin and pregnancy-associated plasma protein A (PAPP-A) were measured at 11–13 weeks’ gestation in 50 singleton normotensive pregnancies that delivered SGA neonates and 300 non-SGA controls. The median adiponectin and PAPP-A levels in the SGA and non-SGA groups, expressed as multiple of the unaffected median (MoM), were compared. Results: The distribution of serum adiponectin was made gaussian by square root (sqrt) transformation. Regression analysis in the non-SGA group demonstrated that for sqrt adiponectin a significant independent contribution was provided by maternal age, weight, smoking status, African and South-Asian racial origin. Each value in the SGA and non-SGA group was then converted into a multiple of the non-SGA median (MoM) after adjustment for maternal characteristics. In the SGA group, compared to the non-SGA controls, median maternal serum PAPP-A was decreased (0.79, interquartile range [IQR] 0.54–1.06 MoM vs. 1.00, IQR 0.71–1.39 MoM) but adiponectin MoM was not significantly different (0.89, IQR 0.65–1.31 MoM vs. 1.02, IQR 0.70–1.29 MoM). Conclusion: Maternal serum adiponectin is not a useful biochemical marker for early prediction of SGA.

Case-control study of passive smoking and the risk of small-for-gestational-age at term.

There is concern about the effects of passive smoking during pregnancy on fetal growth. The authors conducted a case-control study of the association of maternal exposure to passive smoking during pregnancy and the risk of term small-for-gestational-age (SGA) infants in a population of white women who did not smoke during pregnancy and had only a small percentage of users of illegal drugs and alcohol. A total of 111 cases, defined as singleton term (> or = 37 weeks) infants with birth weights < or = 10th percentile for gestational age were compared with 124 term, non-SGA controls. All were identified from Contra Costa, California birth certificates for January 1-September 30, 1991. Subjects were interviewed face-to-face to collect information on exposure to passive smoking during pregnancy. The estimated relative risk for term SGA in association with passive smoke exposure during pregnancy was not increased (> or = 30 hours: odds ratio (OR) = 0.41, 95% confidence interval (Cl) 0.12-1.29) and the risk of term SGA did not increase with increasing hours of exposure to passive smoking. Controlling for parity, weight gain, prepregnancy weight, maternal age, prenatal care, education, income, alcohol consumption, and work during pregnancy in multivariate analysis did not change the findings (> or = 30 hours: OR = 0.47, 95% Cl 0.13-1.69). In this study, maternal exposure to passive smoking during pregnancy was not associated with an increased risk of term SGA. Although difficulties in precisely assessing exposure limit these findings, they should provide some reassurance to women who cannot avoid passive exposure to cigarette smoking during pregnancy.