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Background The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. Methods Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. Results Overall, 5874 studies were identified and 23 were included ( n  = 1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. Conclusions Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

Background & objectives: A etiologically symmetric and asymmetric small for gestational age (SGA) infants are two distinct entities. In view of absence of longitudinal information on growth pattern of skinfold thicknesses (SFTs) among Indian infants, this study was conducted to assess the auxological dynamics of SFTs (sub-cutaneous fat) of symmetric and asymmetric SGA infants. Methods: Triceps, sub-scapular, biceps, mid-axillary and anterior thigh SFTs among full-term, 100 symmetric SGA, 100 asymmetric SGA and 100 appropriate for gestational age (AGA) infants were measured at one, three, six, nine and 12 months. Ponderal Index (PI) was used to categorize infants into symmetric SGA (PI ≥2.2 g/cm3) and asymmetric SGA (PI <2.2 g/cm3). Intra-group (symmetric vs. asymmetric), inter-group (SGA vs. AGA) and gender differences were quantified. Results: SFTs among symmetric, asymmetric SGA infants increased to attain peak by six months. Maximum fat deposition in SGA infants was noticed for triceps, minimum for mid-axillary SFT. Mean triceps and sub-scapular skinfolds were measured higher in symmetric SGA than in asymmetric infants. SGA infants had significantly (P≤0.05) thinner SFTs than AGA. Growth velocity for SFTs, among symmetric and asymmetric SGA, was measured maximum between one and three months, threreafter it declined and relatively, steepness of fall was maximum for mid-axillary SFT followed by sub-scapular SFT. Interpretation & conclusions: Thinner SFTs obtained for symmetric and asymmetric SGA as compared to AGA infants reveal their compromised adiposity and nutritional status. Comparatively, higher SFTs in symmetric than in asymmetric SGA infants appear to suggest that the former have a tendency to accumulate more fat, than the latter during infancy.

To explore the joint and independent effects of gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) on pregnancy outcomes in a population of Chinese Han women and to evaluate pregnant women's adherence to the 2009 Institute of Medicine (IOM) gestational weight gain guidelines. This was a multicenter, retrospective cohort study of 48,867 primiparous women from mainland China who had a full-term singleton birth between January 1, 2011 and December 30, 2011. The independent associations of pre-pregnancy BMI, GWG and categories of combined pre-pregnancy BMI and GWG with outcomes of interest were examined using an adjusted multivariate regression model. In addition, women with pre-pregnancy hypertension were excluded from the analysis of the relationship between GWG and delivery of small-for-gestational-age (SGA) infants, and women with gestational diabetes (GDM) were excluded from the analysis of the relationship between GWG and delivery of large-for-gestational-age (LGA) infants. Only 36.8% of the women had a weight gain that was within the recommended range; 25% and 38.2% had weight gains that were below and above the recommended range, respectively. The contribution of GWG to the risk of adverse maternal and fetal outcomes was modest. Women with excessive GWG had an increased likelihood of gestational hypertension (adjusted OR 2.55; 95% CI = 1.92-2.80), postpartum hemorrhage (adjusted OR 1.30; 95% CI = 1.17-1.45), cesarean section (adjusted OR 1.31; 95% CI = 1.18-1.36) and delivery of an LGA infant (adjusted OR 2.1; 95% CI = 1.76-2.26) compared with women with normal weight gain. Conversely, the incidence of GDM (adjusted OR 1.64; 95% CI = 1.20-1.85) and SGA infants (adjusted OR 1.51; 95% CI = 1.32-1.72) was increased in the group of women with inadequate GWG. Moreover, in the obese women, excessive GWG was associated with an apparent increased risk of delivering an LGA infant. In the women who were underweight, poor weight gain was associated with an increased likelihood of delivering an SGA infant. After excluding the mothers with GDM or gestational hypertension, the ORs for delivery of LGA and SGA infants decreased for women with high GWG and increased for women with low GWG. GWG above the recommended range is common in this population and is associated with multiple unfavorable outcomes independent of pre-pregnancy BMI. Obese women may benefit from avoiding weight gain above the range recommended by the 2009 IOM. Underweight women should avoid low GWG to prevent delivering an SGA infant. Pregnant women should therefore be monitored to comply with the IOM recommendations and should have a balanced weight gain that is within a range based on their pre-pregnancy BMI.

Compared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors. This registry-based cohort study with nationwide data from Denmark (1994-2014), Norway (1988-2015), and Sweden (1988-2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (<37 weeks, versus ≥37), and very preterm birth (<32 weeks, versus ≥32). Singletons born after fresh-ET had lower mean birthweight (-51 g, 95% CI -58 to -45, p < 0.001) and increased odds of small for gestational age (odds ratio [OR] 1.20, 95% CI 1.08 to 1.34, p < 0.001), while those born after frozen-ET had higher mean birthweight (82 g, 95% CI 70 to 94, p < 0.001) and increased odds of large for gestational age (OR 1.84, 95% CI 1.56 to 2.17, p < 0.001), compared to naturally conceived siblings. Conventional population analyses gave similar results. Compared to naturally conceived siblings, mean gestational age was lower after fresh-ET (-1.0 days, 95% CI -1.2 to -0.8, p < 0.001), but not after frozen-ET (0.3 days, 95% CI 0.0 to 0.6, p = 0.028). There were increased odds of preterm birth after fresh-ET (OR 1.27, 95% CI 1.17 to 1.37, p < 0.001), and in most models after frozen-ET, versus naturally conceived siblings, with somewhat stronger associations in population analyses. For very preterm birth, population analyses showed increased odds for both fresh-ET (OR 2.03, 95% CI 1.90 to 2.12, p < 0.001) and frozen-ET (OR 1.66, 95% CI 1.42 to 1.94, p < 0.001) compared with natural conception, but results were notably attenuated within siblings (OR 1.18, 95% CI 1.0 to 1.41, p = 0.059, and OR 0.92, 95% CI 0.67 to 1.27, p = 0.6, for fresh-ET and frozen-ET, respectively). Sensitivity analyses in full siblings, in siblings born within 3-year interval, by birth order, and restricting to single embryo transfers and blastocyst transfers were consistent with the main analyses. Main limitations were high proportions of missing data on maternal body mass index and smoking. We found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias. ClinicalTrials.gov ISRCTN11780826.

Low Birth Weight (LBW) is a surrogate for fetal undernutrition and is associated with impaired nephron development in utero. In this study, we investigate whether having been born LBW and/or small for gestational age (SGA) predict progression to ESRD in IgA nephropathy (IgAN) patients. Retrospective registry-based cohort study. The Medical Birth Registry has recorded all births since 1967 and the Norwegian Renal Registry has recorded all patients with ESRD since 1980. Based on data from the Norwegian Kidney Biopsy Registry we included all patients diagnosed with IgAN in Norway from 1988-2013. These registries were linked and we analysed risk of progression to ESRD associated with LBW (defined as birth weight less than the 10th percentile) and/or SGA (defined as birth weight less than the 10th percentile for gestational week) by Cox regression statistics. We included 471 patients, of whom 74 developed ESRD. As compared to patients without LBW, patients with LBW had a hazard ratio (HR) of 2.0 (95% confidence interval 1.1-3.7) for the total cohort, 2.2 (1.1-4.4) for males and 1.3 (0.30-5.8) for females. Corresponding HRs for SGA were 2.2 (1.1-4.2), 2.7 (1.4-5.5) and 0.8 (0.10-5.9). Further analyses showed that as compared to patients with neither LBW nor SGA, patients with either SGA or LBW did not have significantly increased risks (HRs of 1.3-1.4) but patients who were both LBW and SGA had an increased risk (HR 3.2 (1.5-6.8). Mean duration of follow-up only 10 years and maximum age only 46 years. Among IgAN patients, LBW and/or SGA was associated with increased risk for progression to ESRD, the association was stronger in males.

Children born small for gestational age (SGA) generally have a catch-up growth and rapid weight gain in the first years of life, which is a high risk of insulin resistance and cardiovascular diseases later in life. It was reported that the level of imprinted genes IGF-2, CDKN1C and PHLDA2 regulates placental growth. We assessed these imprinted genes expression levels in placental tissue and their influences on catch-up growth of full-term SGA infants. The protein and mRNA levels of placental CDKN1C, PHLDA2 and IGF-2 were analyzed in 29 full-term SGA and 29 full-term infants born appropriate for gestational age (AGA) using quantitative RT-PCR and Western blot assay, respectively. Catch-up growth was indicated by increased standard deviation score (ΔSDS) of weight at 1, 3 and 6 months relative to birth weight (BW). Correlations between indicated variables were evaluated using Pearson correlation coefficient analysis. Compared to AGA infants, CDKN1C and PHLDA2 levels were significantly increased, whereas IGF-2 was significantly reduced in SGA infants. The value of ΔSDS was significantly higher in SGA than that in AGA infants. For SGA status, Pearson analysis shows i) a negative correlation of CDKN1C and PHLDA2 abundances with BW, and a positive correlation of IGF-2 with BW, ii) no correlation between the three imprinted gene abundances and placental weight (PW), and between PW and BW, iii) a positive correlation of PHLDA2 abundance with CDKN1C, and iv) a positive correlation of CDKN1C and PHLDA2 abundances with ΔSDS, and a negative correlation of IGF-2 with ΔSDS at 1, 3 and 6 months. Taken together, increased CDKN1C and PHLDA2 and reduced IGF-2 abundances in placental tissue were related to BW and early period catch-up growth in full-term SGA infants. Placental CDKN1C, PHLDA2 and IGF-2 level monitoring may be useful for predicting and preventing the development of SGA.

Controversy exists about how much, if any, weight obese pregnant women should gain. While the revised Institute of Medicine guidelines on gestational weight gain (GWG) in 2009 recommended a weight gain of 5-9 kg for obese pregnant women, many studies suggested even gestational weight loss (GWL) for obese women. A systematic review was conducted to summarize pregnancy outcomes in obese women with GWL compared to GWG within the 2009 Institute of Medicine guidelines (5-9 kg). Five databases were searched from 1 January 2009 to 31 July 2014. The Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Statement were followed. A modified version of the Newcastle-Ottawa scale was used to assess individual study quality. Small for gestational age (SGA), large for gestational age (LGA) and preterm birth were our primary outcomes. Six cohort studies were included, none of which assessed preterm birth. Compared to GWG within the guidelines, women with GWL had higher odds of SGA <10th percentile (adjusted odds ratio [AOR] 1.76; 95% confidence interval [CI] 1.45-2.14) and SGA <3rd percentile (AOR 1.62; 95% CI 1.19-2.20) but lower odds of LGA >90th percentile (AOR 0.57; 95% CI 0.52-0.62). There was a trend towards a graded relationship between SGA <10th percentile and each of three obesity classes (I: AOR 1.73; 95% CI 1.53-1.97; II: AOR 1.63; 95% CI 1.44-1.85 and III: AOR 1.39; 95% CI 1.17-1.66, respectively). Despite decreased odds of LGA, increased odds of SGA and a lack of information on preterm birth indicate that GWL should not be advocated in general for obese women.

Prenatal heavy metals exposure has shown a negative impact on birth weight. However, their influence on different clinical forms of fetal smallness was never assessed. To investigate whether there is a differential association between heavy metals exposure and fetal smallness subclassification into intrauterine growth restriction (IUGR) and small-for-gestational age (SGA). In this prospective case-control study, we included 178 mother-infant pairs; 96 of appropriate for gestational age (AGA) and 82 of small fetuses diagnosed in third trimester. The small ones were further subclassified into IUGR, n = 49 and SGA, n = 33. Cadmium (Cd), mercury (Hg), lead (Pb), arsenic (As) and zinc (Zn) levels were measured in the maternal and cord serum, and in the placentas of the three groups. Maternal serum level of Cd (p<0.001) was higher in the small fetuses compared to AGA. Fetal serum level of Cd (p<0.001) was increased in the small fetuses compared to AGA. Fetal serum level of Hg (p<0.05) showed an increase in SGA compared to both IUGR and AGA. Fetal serum level of Zn was increased in the AGA (p < 0.001) compared to each of the small fetuses groups. Only differences in the levels between the small fetuses' subgroups were detected in the fetal serum levels of Cd and Hg. Fetal birth weight was negatively correlated with the fetal serum level of Cd (p < 0.001). No differences in the placental heavy metal levels were observed among the groups. Fetal serum levels of Cd showed differential correlation between small fetuses' clinical subclassification, which together with the increased Cd levels in both maternal and fetal serum of the small fetuses reinforce the negative influence of heavy metals on birth weight. These findings provide more opportunities to verify the role of heavy metals exposure in relation to small fetuses' subclassification.

Small newborns are vulnerable to mortality and lifelong loss of human capital. Measures of vulnerability previously focused on liveborn low-birthweight (LBW) babies, yet LBW reduction targets are off-track. There are two pathways to LBW, preterm birth and fetal growth restriction (FGR), with the FGR pathway resulting in the baby being small for gestational age (SGA). Data on LBW babies are available from 158 (81%) of 194 WHO member states and the occupied Palestinian territory, including east Jerusalem, with 113 (58%) having national administrative data, whereas data on preterm births are available from 103 (53%) of 195 countries and areas, with only 64 (33%) providing national administrative data. National administrative data on SGA are available for only eight countries. Global estimates for 2020 suggest 13·4 million livebirths were preterm, with rates over the past decade remaining static, and 23·4 million were SGA. In this Series paper, we estimated prevalence in 2020 for three mutually exclusive types of small vulnerable newborns (SVNs; preterm non-SGA, term SGA, and preterm SGA) using individual-level data (2010–20) from 23 national datasets (∼110 million livebirths) and 31 studies in 18 countries (∼0·4 million livebirths). We found 11·9 million (50% credible interval [Crl] 9·1–12·2 million; 8·8%, 50% Crl 6·8–9·0%) of global livebirths were preterm non-SGA, 21·9 million (50% Crl 20·1–25·5 million; 16·3%, 14·9–18·9%) were term SGA, and 1·5 million (50% Crl 1·2–4·2 million; 1·1%, 50% Crl 0·9–3·1%) were preterm SGA. Over half (55·3%) of the 2·4 million neonatal deaths worldwide in 2020 were attributed to one of the SVN types, of which 73·4% were preterm and the remainder were term SGA. Analyses from 12 of the 23 countries with national data (0·6 million stillbirths at ≥22 weeks gestation) showed around 74% of stillbirths were preterm, including 16·0% preterm SGA and approximately one-fifth of term stillbirths were SGA. There are an estimated 1·9 million stillbirths per year associated with similar vulnerability pathways; hence integrating stillbirths to burden assessments and relevant indicators is crucial. Data can be improved by counting, weighing, and assessing the gestational age of every newborn, whether liveborn or stillborn, and classifying small newborns by the three vulnerability types. The use of these more specific types could accelerate prevention and help target care for the most vulnerable babies.

Small-for-gestational-age (SGA) infants exhibit considerable heterogeneity in growth trajectories and metabolic outcomes; however, the metabolic basis underlying these variations remains incompletely understood. In this study, we analyzed umbilical cord serum samples from term infants (n = 52; SGA infants, n = 18; appropriate-for-gestational-age controls, n = 34) using gas chromatography–mass spectrometry to explore metabolic profiles. Multivariate and univariate analyses revealed that SGA infants exhibited significantly altered levels of metabolites involved in galactose metabolism, lactose degradation, and multiple pathways related to carbohydrate and energy metabolism. Further subgroup analysis demonstrated that SGA infants with both low weight and short birth length displayed distinct alterations in amino acid metabolism compared to SGA infants with preserved birth length, involving pathways related to glycine, serine, urea cycle, ammonia recycling, and glutathione metabolism. Among these, glutamine showed consistent changes across multiple analytic approaches. These findings suggest that metabolic subclassification based on birth-body proportionality may help identify distinct metabolic phenotypes in SGA infants. Such profiles may serve as early biomarkers of growth potential or future metabolic risk, highlighting the potential for targeted interventions in at-risk subgroups.