Risk Of Large For Gestational Age Research Articles

Association of maternal body mass index change with risk of large for gestational age among pregnant women with and without gestational diabetes mellitus: a retrospective cohort study

Objective To investigate the associations of body mass index (BMI) change and large for gestational age (LGA) among prepregnancy normal-weight women with and without gestational diabetes mellitus (GDM). Methods The retrospective study including 9515 normal-weight pregnant women (1331 women with GDM and 8184 without GDM) was conducted in Fujian Maternity and Child Health Hospital in 2020. The BMI change was calculated as gestational weight gain in kilograms by maternal height in meters. The binary logistic regression, stratified analyses, restricted cubic spline models and additive interaction analysis were adopted to reveal the relationship between BMI change and LGA. Results Pregnant women with GDM had a lower level of BMI change but a higher incidence of LGA compared with those without GDM. After adjustment for covariates variables, we found that the risk of LGA was associated with the highest quartile of BMI change (OR = 1.89, 95%CI:1.27–2.8 for GDM and OR = 1.48,95%CI:1.27–1.75 for non-GDM). There were significant linear relationships of BMI change and LGA with the inflection point of 5.096 and 5.401 kg/m2 in GDM and non-GDM groups. Significant additive interaction was observed between parity and BMI change level concerning LGA. A significant difference in BMI change and gestational weight gain (GWG) for LGA prediction was detected. Conclusion Higher BMI changes were significantly associated with a higher risk of LGA in pregnant women with or without GDM in a linear dose-response relationship, with the threshold around 5.096 and 5.401 kg/m2, respectively. These suggested that BMI changes may be a useful predictor for the incidence of LGA in singleton pregnant women.

Association of duration of embryo culture with risk of large for gestational age delivery in cryopreserved embryo transfer cycles

To examine the relationship between the day of embryo cryopreservation and large for gestational age (LGA) infants in women undergoing frozen embryo transfers (FETs) after cryopreservation on days 2-7 after fertilization and to compare the risk of the day of embryo cryopreservation to other possible risk factors of LGA after FET cycles. Retrospective cohort study. Society of Assisted Reproduction Clinical Outcomes Reporting System. Women undergoing FET cycles. Day of cryopreservation. Singleton LGA infant. A total of 33,030 (18.2%) FET cycles in the study group (n = 181,592) resulted in LGA infants during the study period of 2014-2019. There was an increase in LGA risk when cryopreservation was performed from day 2 (13.7%) to days 3-7 (14.4%, 15.0%, 18.2%, 18.5%, and 18.9%). In the log-binomial model, the risk increased compared with days 2-3 combined when cryopreservation was performed on days 5-7 (adjusted relative risk [aRR] 1.32, 95% confidence interval [CI] 1.22-1.44 for day 5, aRR 1.34, 95% CI 1.23-1.46 for day 6, and aRR 1.42, 95% CI 1.25-1.61 for day 7). Other factors most associated with LGA risk in the log-binomial model were preterm parity of >3 compared with 0 (aRR 1.82, 95% CI 1.24-2.69) and body mass index (BMI) of >35 kg/m2 compared with normal weight (aRR 1.94, 95% CI 1.88-2.01). Increasing gravity, parity, BMI, number of oocytes, and embryo grade were also associated with LGA in this model. Asian, Black, Hispanic, and combined Hawaiian and Pacific Islander were protective factors in the model compared with White patients. Low BMI (<18.5 kg/m2) was also considered a protective factor in the model compared with normal BMI. Duration of embryo culture was associated with an increased risk of LGA in this study cohort when controlling for known confounders such as maternal BMI and parity. This study sheds new light on the possible link between FET and LGA infants.

Elevated serum uric acid to creatinine ratio is associated with adverse pregnancy outcomes: a prospective birth cohort study.

Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.

Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis

BackgroundPerinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM.MethodsSystematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA).ResultsA total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers.ConclusionsMaternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Preconception dietary glycemic index and risk for large-for-gestational age births

ObjectivesDiets with a high glycemic index (GI) leading to elevated postprandial glucose levels and hyperinsulinemia during pregnancy have been inconsistently linked to an increased risk for large-for-gestational-age (LGA) births. The effects of prepregnancy dietary GI on LGA risk are, to our knowledge, unknown. We examined the association of prepregnancy dietary GI with LGA births and joint associations of GI and maternal overweight/obesity and infant sex with LGA births among 10 188 infants born without congenital anomalies from 1997 to 2011, using data from the National Birth Defects Prevention Study (NBDPS). The aim of this study was to investigate this association among infants without major congenital anomalies (controls) who participated in the NBDPS and to evaluate how prepregnancy BMI and infant sex may modify this association on the additive scale. MethodsDietary intake was ascertained using a 58-item food frequency questionnaire. We dichotomized dietary GI into high and low categories using spline regression models. Infants with a birth weight at or above the 90th percentile for gestational age and sex, according to a U.S. population reference, were considered LGA. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs). ResultsOf the infants, 859 (9%) had a high dietary GI (cut-point: 59), and 1244 infants (12%) were born LGA. Unadjusted analysis suggested an inverse association between high dietary GI and LGA (OR, 0.79; 95% CI, 0.62–0.99). No association was observed in multivariable models when comparing high dietary GI intake between LGA births and all other births (OR, 0.94; 95% CI, 0.74–1.20) or when excluding small-for-gestational-age (SGA) births (OR, 0.94; 95% CI, 0.73–1.19). No joint associations with maternal overweight/obesity or infant sex were observed. ConclusionHigh prepregnancy maternal GI was not associated with LGA births independently of or jointly with other factors.

Association of Triglyceride-Glucose Index with Risk of Large for Gestational Age: A Prospective Cohort Study.

To evaluate the association of the baseline triglyceride-glucose (TyG) index in the first trimester of pregnancy with the risk of large for gestational age (LGA) in Southeast Chinese pregnant women. A prospective birth cohort study recruiting 12,108 pregnant women at their first prenatal visit before 13 gestation weeks was conducted in 2019-2022. Baseline characteristics were collected from medical records or using questionnaires and blood samples were collected in the first trimester. The TyG index was obtained through the formula: ln[triglyceride (mg/dl)×fasting plasma glucose (mg/dl)/2]. The binary logistic regression model was performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) to reveal the relationship between TyG index and LGA. Receiver-operating characteristic curve analysis was conducted to evaluate the ability of the TyG index to predict the risks of LGA. The overall incidence of LGA in the current study was 11.4% and the incidence of LGA increased with the baseline TyG index increasing. The risk of LGA was 2.05 (1.64, 2.57) for per unit increase in baseline TyG index. The increasing trend was found across the TyG index quartiles and the highest TyG quartiles raised the risk of LGA to 1.86 (95% CI: 1.51, 2.27) compared to the bottom TyG quartiles after full adjustment. The risk of LGA remained positive after stratification analysis. The AUC was 0.584 (95% CI: 0.569~0.600) in the entire subject, and the threshold was 8.34, with a sensitivity of 0.74 and specificity of 0.38. The findings suggested that a higher TyG index in the first trimester was independently associated with higher risk of LGA and high TyG index in the first trimester may play as a early predictor for LGA.

Effects of prepregnancy dietary patterns on infant birth weight: a prospective cohort study

Background Maternal nutrition can have a profound effect on fetal growth, development, and subsequent infant birth weight. However, little is known regarding the influence of prepregnancy dietary patterns. Objectives This study aimed to explore the effects between prepregnancy dietary patterns on birth weight. Methods This study included 911 singleton live-born infants from the Taicang and Wuqiang Mother–Child Cohort Study (TAWS). Baseline information and prepregnancy diet data were collected during early pregnancy. Newborn birth information was obtained from the Wuqiang County Hospital. Macrosomia, defined as a birth weight of ≥4000 g, and large for gestational age (LGA), defined as a birth weight higher than the 90th percentile for the same sex and gestational age, were the outcomes of interest. The dietary patterns were extracted using principal component analysis. Logistic regression models were used to investigate the association between prepregnancy dietary patterns (in tertiles) and macrosomia and LGA, and subgroup analysis was further explored by pre-pregnancy body mass index (BMI). Results Four dietary patterns were identified based on 15 food groups. These patterns were named as “cereals–vegetables–fruits,” “vegetables–poultry–aquatic products,” “milk–meat–eggs,” and “nuts–aquatic products–snacks.” After adjusting for sociodemographic characteristics, pregnancy complications, and other dietary patterns, greater adherence to the “cereals–vegetables–fruits” pattern before pregnancy was associated with a higher risk of macrosomia (adjusted OR = 2.220, 95% CI: 1.018, 4.843), while greater adherence to the “nuts–aquatic products–snacks” pattern was associated with a lower risk of macrosomia (adjusted OR = 0.357, 95% CI: 0.175, 0.725) compared to the lowest tertile. No significant association was observed between prepregnancy dietary patterns and LGA. However, after subgroup analysis of pre-pregnancy BMI, “cereals–vegetables–fruits” pattern was associated with an increased risk of LGA in overweight and obese mothers (adjusted OR = 2.353, 95% CI: 1.010, 5.480). Conclusions An unbalanced pre-pregnancy diet increases the risk of macrosomia and LGA, especially in overweight or obese women before pre-pregnancy.

Association between gestational weight gain and adverse neonatal outcomes in women conceiving with assisted reproductive technology: Evidence from the NVSS 2019-2021.

To evaluate the association between gestational weight gain (GWG) and adverse neonatal outcomes in women who conceived using assisted reproductive technology (ART). The National Vital Statistics System (NVSS) 2019-2021 provided data for this retrospective cohort study. Adverse neonatal outcomes included premature birth, small for gestational age (SGA), large for gestational age (LGA), macrosomia, low birth weight (LBW), and other abnormal conditions. Any adverse outcome was defined as at least one of the above six outcomes. Multivariate logistic regression analysis was employed to evaluate the associations between GWG and different outcomes, after adjusting for confounding factors. These associations were further assessed in subgroups of maternal age at delivery, paternal age at delivery, preconception body mass index (BMI), gestational age, maternal race, parity, gestational diabetes, and gestational hypertension. Totally 108201 women were included, with 22282 in the insufficient GWG group, 38034 in the sufficient GWG group, and 47885 in the excessive GWG group. Women with insufficient GWG [odds ratios (OR) = 1.11, 95%CI: 1.07-1.16, P<0.001] and excessive GWG (OR = 1.14, 95%CI: 1.10-1.18, P<0.001) had significantly greater risks of any adverse outcome than those with sufficient GWG. In contrast to sufficient GWG, insufficient GWG was associated with significantly elevated risks of premature birth (OR = 1.42, 95%CI: 1.35-1.48, P<0.001), SGA (OR = 1.45, 95%CI: 1.37-1.53, P<0.001), LBW (OR = 1.47, 95%CI: 1.37-1.58, P<0.001), and other abnormal conditions (OR = 1.32, 95%CI: 1.27-1.39, P<0.001), and excessive GWG was associated with significantly lower risks of premature birth (OR = 0.86, 95%CI: 0.83-0.90, P<0.001), SGA (OR = 0.79, 95%CI: 0.75-0.83, P<0.001), LBW (OR = 0.85, 95%CI: 0.79-0.91, P<0.001), and other abnormal conditions (OR = 0.92, 95%CI: 0.88-0.96, P<0.001). Infants born to women with insufficient GWG had significantly decreased risks of LGA (OR = 0.71, 95%CI: 0.66-0.75, P<0.001) and macrosomia (OR = 0.68, 95%CI: 0.63-0.74, P<0.001), and infants born to women with excessive GWG had significantly increased risks of LGA (OR = 1.50, 95%CI: 1.44-1.56, P<0.001) and macrosomia (OR = 1.60, 95%CI: 1.51-1.69, P<0.001). Insufficient GWG and excessive GWG were associated with increased risks of any adverse outcome than sufficient GWG in women who conceived with ART, indicating the applicability of recommended GWG by the Institute of Medicine (IOM) in this population.

The relationship between gut microbiota, short-chain fatty acids, and glucolipid metabolism in pregnant women with large for gestational age infants.

To elucidate the association between gut microbiota, short-chain fatty acids (SCFAs), and glucolipid metabolism in women with large for gestational age (LGA) infants. A single-center, observational prospective cohort study was performed at a tertiary hospital in Wenzhou, China. Normal pregnant women were divided into LGA group and appropriate for gestational age (AGA) group according to the neonatal birth weight. Fecal samples were collected from each subject before delivery for the analysis of gut microbiota composition (GMC) and SCFAs. Blood samples were obtained at 24-28 weeks of gestation age to measure fasting blood glucose and fasting insulin levels, as well as just before delivery to assess serum triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. The GMC exhibited differences at various taxonomic levels. Within the Firmicutes phylum, genus Lactobacillus, genus Clostridium, species Lactobacillus agil, and species Lactobacillus salivarius were enriched in the LGA group. Microbispora at genus level, Microbispora rosea at species level belonging to the Actinobacteria phylum, Neisseriales at order level, Bartonellaceae at family level, Paracoccus aminovorans, and Methylobacterium at genus level from the Proteobacteria phylum were more abundant in the LGA group. In contrast, within the Bacteroidetes phylum, Prevotella at genus level and Parabacteroides distasonis at species level were enriched in the AGA group. Although there were few differences observed in SCFA levels and most glucolipid metabolism indicators between the two groups, the serum HDL level was significantly lower in the LGA group compared to the AGA group. No significant relevance among GMC, SCFAs, and glucolipid metabolism indicators was found in the LGA group or in the AGA group. Multiple different taxa, especially phylum Firmicutes, genus Prevotella, and genus Clostridium, might play an important role in excessive fetal growth, and LGA might be associated with the lower serum HDL level.

Gestational weight loss and fetal growth in uncomplicated pregnancies among women with obesity: a population-based retrospective cohort study

ObjectiveThe impact of gestational weight loss (GWL) on fetal growth among women with obesity remains unclear. This study aimed to examine the association between weight loss during pregnancy among women with body mass index (BMI) ≥ 30 kg/m2 and the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) neonates.MethodsWe conducted a retrospective, population-based cohort study of women with pre-pregnancy obesity that resulted in a singleton live birth in 2012-2017, using birth registry data in Ontario, Canada. Women with pregnancy complications or health conditions which could cause weight loss were excluded. GWL is defined as negative gestational weight change (≤0 kg). The association between GWL and fetal growth was estimated using generalized estimating equation models and restricted cubic spline regression analysis. Stratified analysis was conducted by obesity class (I:30–34.9 kg/m2, II:35–39.9 kg/m2, and III + : ≥40 kg/m2).ResultsOf the 52,153 eligible women who entered pregnancy with a BMI ≥ 30 kg/m2, 5.3% had GWL. Compared to adequate gestational weight gain, GWL was associated with an increased risk of SGA neonates (aRR:1.45, 95% CI: 1.30–1.60) and a decreased risk of LGA neonates (aRR: 0.81, 95% CI:0.73–0.93). Non-linear L-shaped associations were observed between gestational weight change and SGA neonates, with an increased risk of SGA observed with increased GWL. On the contrary, non-linear S-shaped associations were observed between gestational weight change and LGA neonates, with a decreased risk of LGA observed with increased GWL. Similar findings were observed from the stratified analysis by obesity class.ConclusionThese findings highlight that GWL in women with obesity may increase the risk of SGA neonates but reduce the risk of LGA neonates. Recommendations of GWL for women with obesity should be interpreted with caution.

Letrozole use in vitrified single-blastocyst transfer cycles is associated with lower risk of large for gestational age infants in patients with polycystic ovary syndrome.

To evaluate the obstetric and perinatal outcomes of three routine endometrial preparation protocols in women with PCOS who underwent frozen embryo transfer (FET). This was a retrospective study in women with PCOS who underwent FET in an academic reproductive medical center. A total of 2710 cycles were enrolled and classified into three groups according to different endometrial preparation protocols; human menopausal gonadotropin (HMG), letrozole + HMG, or hormone replacement therapy (HRT). The stimulation groups had reduced risks of hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) infants, and cesarean delivery than the HRT group. After adjustment for different confounder combinations in the two models, the frequencies of LGA and HDP in the letrozole + HMG group and the HMG group were still significantly lower than those in the HRT group. The letrozole + HMG group exhibited a reduced risk of LGA than HMG group after adjustment of confounders. A trend toward risk reductions in HDP and LGA was observe in turns of HRT, HMG, and letrozole + HMG groups, and the trends were statistically significant (Ptrend = 0.031 and 0.001). In patients with PCOS, ovarian stimulation protocols for endometrial preparation are associated with reduced risks of HDP and LGA compared to HRT cycles. The use of letrozole could further reduce risk of LGA compared to HMG only protocol. We propose that ovarian stimulation protocols can be used widely for endometrial preparation in FET cycles in women with PCOS, especially with the use of letrozole.

Birth outcomes in mothers with hypertensive disorders and polycystic ovary syndrome: a population-based cohort study.

Is polycystic ovary syndrome (PCOS) associated with higher risks of extreme birth size and/or preterm birth in mothers with different hypertension types? PCOS was associated with additional risks of preterm birth in mothers with chronic hypertension and in singleton pregnancies of mothers with pre-eclampsia, and with higher risks of offspring born large for gestational age (LGA) in mothers with gestational hypertension. Women with PCOS are more likely to develop gestational hypertension, pre-eclampsia, and chronic hypertension. Although adverse birth outcomes have been frequently reported in mothers with PCOS, such associations in the setting of a hypertensive disorder remain unknown. This is a population-based cohort study including all live births 2004-2014 in Finland (n = 652 732). To ensure diagnosis specificity, mothers with diagnoses that could cause signs and symptoms resembling PCOS were excluded. Maternal diagnoses of PCOS, gestational hypertension, chronic hypertension, and pre-eclampsia were identified from the Finnish national registries. Generalized estimating equation and multivariable logistic regression were used to assess the adjusted odds ratio (aOR) and 95% CIs of preterm birth, very preterm birth, and offspring being small for gestational age (SGA) or LGA in hypertensive mothers with or without PCOS, using normotensive mothers without PCOS as reference. Of 43 902 (6.7%) mothers with hypertensive disorders, 1709 (3.9%) had PCOS. Significant interactions were detected for PCOS with hypertension on preterm birth, very preterm birth, offspring born SGA and LGA (Fpreterm = 504.1, Pinteraction < 0.001; Fvery preterm = 124.2, Pinteraction < 0.001; FSGA = 99.5, Pinteraction < 0.001; FLGA = 2.7, Pinteraction = 0.012, respectively). Using mothers with no hypertensive disorder and no PCOS as reference, the risks of preterm and very preterm birth were overrepresented in non-PCOS mothers with chronic hypertension or pre-eclampsia. PCOS was associated with higher risks of preterm birth (aORPCOS 4.02, 3.14-5.15 vs aORnon-PCOS 2.51, 2.32-2.71) in mothers with chronic hypertension, with significant interaction between the exposures (F = 32.7, Pinteraction < 0.001). PCOS was also associated with a higher risk of preterm birth in singleton pregnancies of mothers with pre-eclampsia (aORPCOS 7.33, 5.92-9.06 vs aORnon-PCOS 5.72, 5.43-6.03; F = 50.0, Pinteraction < 0.001). Furthermore, the associations of PCOS comorbid with chronic hypertension or pre-eclampsia was detected also for spontaneous births. Moreover, the risk of offspring LGA was higher in mothers with PCOS and gestational hypertension although lower in those with gestational hypertension alone (aORPCOS 2.04, 1.48-2.80 vs aORnon-PCOS 0.80, 0.72-0.89; F = 9.7, Pinteraction = 0.002), whereas for offspring SGA, the risks were comparable between hypertensive mothers with and those without PCOS. Information on medication treatment, gestational weeks of onset for pre-eclampsia and gestational hypertension, weight gain during pregnancy, and PCOS phenotypes were not available. All diagnoses were retrieved from registries, representing only those seeking medical care for their symptoms. The ICD-9 codes used to identify PCOS before year 1996 are known to underestimate the prevalence of PCOS, while the inclusion of anovulatory infertility as PCOS might introduce an overrepresentation bias, although PCOS constitutes 80% of anovulatory infertility. The risk of very preterm birth in relation to maternal PCOS and hypertensive disorders should be interpreted with caution owing to limited sample sizes. Multifetal pregnancies among maternal PCOS were too few for a subgroup analysis. Moreover, ART included IVF/ICSI only. Potential effects of other treatments, such as ovulation induction, were not examined. PCOS was associated with additional risks of preterm birth or offspring being LGA in hypertensive mothers, which varied between hypertension types. The exacerbated risks highlight consideration of PCOS in pregnancy counseling and management for women with hypertensive disorders. This study was supported by Shandong Provincial Natural Science Foundation, China [ZR2020MH064 to X.C.], the joint research funding of Shandong University and Karolinska Institute [SDU-KI-2019-08 to X.C. and C.L.], the Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2022-01188 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [RS2021-0855 to C.L.], the Swedish Brain Foundation [FO2021-0412 to C.L.]. The funders had no role in study design, data collection, analysis, and interpretation, writing of the report or decision to submit for publication. The authors report no conflicts of interest. N/A.

Maternal gestational weight gain and adverse pregnancy outcomes in non-diabetic women

Objective This study investigated the relationship between maternal gestational weight gain (GWG) and the risk of adverse pregnancy outcomes in gestational diabetes mellitus (GDM)-negative pregnant women. Methods We did a retrospective cohort study between 1 July 2017, and 1 January 2020, at Women’s Hospital, Zhejiang University School of Medicine. Firstly, pregnant women were divided into subgroups according to the entire GWG (inadequate GWG, adequate GWG, and excessive GWG) and GDM status (positive and negative) during pregnancy. Secondly, the whole population of pregnant women with GDM was used as a reference to evaluate the relationship between GWG and adverse pregnancy outcomes in GDM-negative pregnant women. Lastly, subgroup analysis was conducted based on pre-pregnancy body mass index (pp-BMI). Results A total of 30,910 pregnant women were analysed. Included pregnancy women were divided into three groups based on GWG: 7569 (24.49%) pregnancy women had inadequate GWG, 13088 (42.34%) had adequate GWG, and 10,253 (33.17%) had excessive GWG. In addition to preterm birth and small for gestational age (SGA), the incidence of macrosomia and large for gestational age (LGA) continues to increase from inadequate GWG to excessive GWG groups. Pregnant women without GDM who have excessive GWG are at higher risk of macrosomia and LGA than pregnant women with GDM. Moreover, this risk increased with increasing pp-BMI. Pregnant women without GDM with inadequate GWG were at risk of preterm birth regardless of pp-BMI. Only those with inadequate GWG and pp-BMI < 18.5 kg/m2 had an increased risk of SGA. Conclusions In conclusion, inappropriate GWG is strongly associated with adverse pregnancy outcomes, even if they do not have GDM. Therefore, this population should receive attention and management before and during pregnancy. Impact Statement What is already known on this subject? Several studies have focused on the GDM population and the risk of adverse pregnancy outcomes, but few have focused on GDM-negative populations. This is because GDM-negative women are perceived to be "safe," leading to less focus on themselves, which can lead to subsequent excessive weight gain during pregnancy. Whether this factor increases the risk of adverse pregnancy outcomes in this population remains unknown. What do the results of this study add? Our study found an inverse relationship between GWG and GDM. Therefore, our study focuses on this group of GDM-negative pregnant women. Their excessive weight gain increases the risk of adverse pregnancy outcomes, even higher than GDM pregnant women. What are the implications of these findings for clinical practice and/or further research? GWG is associated with adverse pregnancy outcomes. Therefore, pregnant women without GDM also need increased attention and management of their weight before and during pregnancy. Prenatal care providers can utilise tools such as diet, exercise counselling, weight tracking, and setting weight gain goals to reduce inappropriate weight gain and mitigate its adverse effects on pregnancy outcomes.

The influence of embryo stage on obstetric complications and perinatal outcomes following programmed compared to natural frozen-thawed embryo transfer cycles: a systematic review and meta-analysis.

To investigate the effect of embryo stage at the time of transfer on obstetric and perinatal outcomes in programmed frozen-thawed embryo transfer (FET) versus natural FET cycles. Systematic review and meta-analysis. Not applicable. Women with programmed frozen-thawed embryo transfer (FET) and natural FET. The PubMed, MEDLINE, and EMBASE databases and the Cochrane Central Register of Controlled Trials (CCRT) were searched from 1983 to October 2022. Twenty-three observational studies were included. The primary outcomes were hypertensive disorders of pregnancy (HDPs), gestational hypertension and preeclampsia (PE). The secondary outcomes were gestational diabetes mellitus (GDM), placenta previa, postpartum haemorrhage (PPH), placental abruption, preterm premature rupture of membranes (PPROM), large for gestational age (LGA), small for gestational age (SGA), macrosomia, and preterm delivery (PTD). The risk of HDP (14 studies, odds ratio (OR) 2.17; 95% confidence interval (CI) 1.95-2.41; P<0.00001; I2 = 43%), gestational hypertension (11 studies, OR 1.38; 95% CI 1.15-1.66; P=0.0006; I2 = 19%), PE (12 studies, OR 2.09; 95% CI 1.88-2.32; P<0.00001; I2 = 0%), GDM (20 studies, OR 1.09; 95% CI 1.02-1.17; P=0.02; I2 = 8%), LGA (18 studies, OR 1.11; 95% CI 1.07-1.15; P<0.00001; I2 = 46%), macrosomia (12 studies, OR 1.15; 95% CI 1.07-1.24; P=0.0002; I2 = 31%), PTD (22 studies, OR 1.21; 95% CI 1.15-1.27; P<0.00001; I2 = 49%), placenta previa (17 studies, OR 1.2; 95% CI 1.02-1.41; P=0.03; I2 = 11%), PPROM (9 studies, OR 1.19; 95% CI 1.02-1.39; P=0.02; I2 = 40%), and PPH (12 studies, OR 2.27; 95% CI 2.02-2.55; P <0.00001; I2 = 55%) were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer. Blastocyst transfer had a higher risk of HDP (6 studies, OR 2.48; 95% CI 2.12-2.91; P<0.00001; I2 = 39%), gestational hypertension (5 studies, OR 1.87; 95% CI 1.27-2.75; P=0.002; I2 = 25%), PE (6 studies, OR 2.23; 95% CI 1.93-2.56; P<0.00001; I2 = 0%), GDM (10 studies, OR 1.13; 95% CI 1.04-1.23; P=0.005; I2 = 39%), LGA (6 studies, OR 1.14; 95% CI 1.07-1.21; P<0.0001; I2 = 9%), macrosomia (4 studies, OR 1.15; 95% CI 1.05-1.26; P<0.002; I2 = 68%), PTD (9 studies, OR 1.43; 95% CI 1.31-1.57; P<0.00001; I2 = 22%), PPH (6 studies, OR 1.92; 95% CI 1.46-2.51; P<0.00001; I2 = 55%), and PPROM (4 studies, OR 1.45; 95% CI 1.14-1.83; P=0.002; I2 = 46%) in programmed FET cycles than in natural FET cycles. Cleavage-stage embryo transfers revealed no difference in HDPs (1 study, OR 0.81; 95% CI 0.32-2.02; P=0.65; I2 not applicable), gestational hypertension (2 studies, OR 0.85; 95% CI 0.48-1.51; P=0.59; I2 = 0%), PE (1 study, OR 1.19; 95% CI 0.58-2.42; P=0.64; I2not applicable), GDM (3 study, OR 0.79; 95% CI 0.52-1.20; P=0.27; I2 = 21%), LGA (1 study, OR 1.15; 95% CI 0.62-2.11; P=0.66; I2not applicable), macrosomia (1 study, OR 1.22; 95% CI 0.54-2.77; P=0.64; I2 not applicable), PTD (2 studies, OR 1.05; 95% CI 0.74-1.49; P=0.79; I2 = 0%), PPH (1 study, OR 1.49; 95% CI 0.85-2.62; P=0.17; I2not applicable), or PPROM (2 studies, OR 0.74; 95% CI 0.46-1.21; P=0.23; I2 = 0%) between programmed FET cycles and natural FET cycles. The risks of HDPs, gestational hypertension, PE, GDM, LGA, macrosomia, SGA, PTD, placenta previa, PPROM, and PPH were increased in programmed FET cycles versus natural FET cycles with overall embryo transfer and blastocyst transfer, but the risks were not clear for cleavage-stage embryo transfer.

The associations of ferritin, serum lipid and plasma glucose levels across pregnancy in women with gestational diabetes mellitus and newborn birth weight

BackgroundWomen with gestational diabetes mellitus (GDM) are at greater risk of abnormal birth weight. Since the level of biochemical indicators could often affect the intrauterine growth and development of the fetus, it is of great practical significance to understand the changes of biochemical levels across pregnancy in women with GDM and to find out the indicators that play an important role in predicting birth weight.MethodsThe data source of this study was from the Xi'an Longitudinal Mother–Child Cohort study (XAMC), in which women with GDM with normal and high pre-pregnancy body mass index (BMI) and their newborns between January 1st and March 31st in 2018 were included. The data of ferritin, serum lipid profile and fasting plasma glucose (FPG) of mothers in the three trimesters of pregnancy, as well as birth weight of newborns were all collected from medical records. Multiple linear regression and multivariate logistic regression analyses were used to explore the association of the biochemical indexes and birth weight. A P value < 0.05 was considered statistically significant.ResultsA total of 782 mother-infant pairs were finally included and divided into normal weight group (NG) (n = 530, 67.8%) and overweight/obesity group (OG) (n = 252, 32.2%) according to maternal pre-pregnancy BMI. The level of ferritin in both NG and OG decreased during pregnancy (P for trend < 0.001 for all), whereas the levels of total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C) and triglycerides (TG) all showed an upward trend (P for trend < 0.05 for all). The levels of FPG in the two groups remained in a relatively stable during the whole pregnancy even though it was higher in OG during the 2nd and 3rd trimesters, whilst HbAlc levels in NG women increased (P for trend = 0.043) during pregnancy. Meanwhile, the risk of macrosomia and large-for-gestational-age (LGA) increased with the increase of FPG level (P for trend < 0.05). Multivariate logistic regression analyses results showed that only FPG level in the 3rd trimester was correlated with birth weight, with birth weight increased by 44.9 g for each SD increase in FPG level.ConclusionMaternal FPG in the 3rd trimester is an independent predictor of newborn birth weight, and a higher level of that is associated with an increased risk of macrosomia and LGA.

Does Iodine Intake Modify the Effect of Maternal Dysglycemia on Birth Weight in Mild-to-Moderate Iodine-Deficient Populations? A Mother-Newborn Prospective Cohort Study.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight among individuals with mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake among pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT) and non-fasting glucose levels that were determined before delivery; individuals' iodine statuses were assessed using an iodine food frequency questionnaire; and serum thyroglobulin (Tg) and urinary iodine concentrations (UIC) were used to assess each group's iodine status. Thyroid antibodies and free thyroxine (FT4) levels were measured. Obstetric and anthropometric data were also collected. Large-for-gestational age (LGA) status was predicted using a Cox proportional hazards model with multiple confounders. Tg > 13 g/L was independently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4-10.2, p = 0.001). Estimated iodine intake correlated with FT4 among participants who reported consuming iodine-containing supplements (ICS) after adjusting for confounders (β = 0.4, 95% CI: 0.0002-0.0008, p = 0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (β = -0.2 95% CI:-0.08--56.49, p = 0.049). We conclude that in mild-to-moderate ID regions, insufficient maternal iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect that maternal dysglycemia has on offspring weight.

P-256 Large for gestational age in singletons born following frozen embryo transfer: due to freezing technique or to endometrial preparation protocol? Lessons from the French registry

Abstract Study question Is large for gestational age (LGA) observed in singletons born following frozen embryo transfers (FET) either due to freezing technique or to endometrial preparation protocol? Summary answer Artificial cycles were associated with a higher rate of LGA when compared to ovulatory cycles, whereas no difference was observed between the freezing techniques. What is known already Several studies compared neonatal outcomes after fresh embryo transfer (fresh ET) and FET, and showed that FET was associated with improved neonatal outcomes, including reduced risks of preterm birth, low birth weight and small for gestational age (SGA) when compared to fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology remains unclear; parental infertility, laboratory procedures including embryo culture conditions and freezing-thawing processes, as well as endometrial preparation treatments might be at play. Study design, size, duration A multicentric epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national registry of in vitro fertilisation (IVF) from 2014 to 2018, including deliveries resulting from fresh ET and FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres including the vitrification media and devices, as well as the endometrial preparation protocols. Participants/materials, setting, methods Data were collected from 35 French fertility centres, leading to the inclusion of a total of 72,789 fresh ET, 10,602 slow-freezing FET and 30,062 vitrification FET cycles. Fetal growth disorders were defined in liveborn singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if &amp;lt; 10th and &amp;gt;90th percentile, respectively. Analyses were performed using linear mixed models with the centres as random effect. Main results and the role of chance Among a total of 26,585 liveborn singletons, 16,413 babies were born from fresh ET, 1,644 from slow-freezing FET and 8,528 from vitrification FET. Birthweight was significantly higher in the FET groups compared to the fresh ET group, with no difference between the two freezing techniques. Likewise, LGA rates were higher and SGA rates were lower in the FET groups compared to the fresh ET group (12.0% vs 6.4%, p &amp;lt; 0.001, and 7.8% vs 13.4%, p &amp;lt; 0.001 respectively). In a multivariable analysis, the risk of LGA following FET was not different between stimulated and natural cycles (adjusted odds ratio: 1.06, 95% confidence interval: 0.83-1.35, p = 0.64) but was significantly increased in artificial compared to natural cycles (aOR 1.36 [1.11-1.67], p = 0.003). On the contrary, the risk of LGA was not associated with either the freezing mode (slow-freezing vs vitrification) or the embryo stage (cleaved embryo vs blastocyst). When focusing on vitrification, the risk of LGA was not associated with either the freezing medium used or the embryo stage, and no difference was observed according to the vitrification device. Limitations, reasons for caution Most of the vitrification techniques were performed using the same device, and with two major vitrification media, limiting the interpretability of the comparison of the risk for LGA according to the device or the vitrification media. Wider implications of the findings Our results seem reassuring regarding potential fetal growth disorders following embryo vitrification in comparison to slow-freezing. Even if other factors may be involved, the impact of the endometrial preparation treatments seems to prevail for LGA risk following FET. FET during ovulatory cycles could minimize the risk for fetal growth disorders. Trial registration number N/A

Treatment of women with mild gestational diabetes mellitus decreases the risk of adverse perinatal outcomes

AimsGlycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia. MethodsWe reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1–5.2 mmol/L, 1 h PG 10.0–10.5 mmol/L, or 2 h PG 8.5–8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B. ResultsThere were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g. ConclusionThe diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.

Neighborhood Food Environment and Birth Weight Outcomes in New York City

Infants born with unhealthy birth weight are at greater risk for long-term health complications, but little is known about how neighborhood characteristics (eg, walkability, food environment) may affect birth weight outcomes. To assess whether neighborhood-level characteristics (poverty rate, food environment, and walkability) are associated with risk of unhealthy birth weight outcomes and to evaluate whether gestational weight gain mediated these associations. The population-based cross-sectional study included births in the 2015 vital statistics records from the New York City Department of Health and Mental Hygiene. Only singleton births and observations with complete birth weight and covariate data were included. Analyses were performed from November 2021 to March 2022. Residential neighborhood-level characteristics, including poverty, food environment (healthy and unhealthy food retail establishments), and walkability (measured by both walkable destinations and a neighborhood walkability index combining walkability measures like street intersection and transit stop density). Neighborhood-level variables categorized into quartiles. The main outcomes were birth certificate birth weight measures including small for gestational age (SGA), large for gestational age (LGA), and sex-specific birth weight for gestational age z-score. Generalized linear mixed-effects models and hierarchical linear models estimated risk ratios for associations between density of neighborhood-level characteristics within a 1-km buffer of residential census block centroid and birth weight outcomes. The study included 106 194 births in New York City. The mean (SD) age of pregnant individuals in the sample was 29.9 (6.1) years. Prevalence of SGA and LGA were 12.9% and 8.4%, respectively. Residence in the highest density quartile of healthy food retail establishments compared with the lowest quartile was associated with lower adjusted risk of SGA (with adjustment for individual covariates including gestational weight gain z-score: risk ratio [RR], 0.89; 95% CI 0.83-0.97). Higher neighborhood density of unhealthy food retail establishments was associated with higher adjusted risk of delivering an infant classified as SGA (fourth vs first quartile: RR, 1.12; 95% CI, 1.01-1.24). The RR for the association between density of unhealthy food retail establishments and risk of LGA was higher after adjustment for all covariates in each quartile compared with quartile 1 (second: RR, 1.12 [95% CI, 1.04-1.20]; third: RR, 1.18 [95% CI, 1.08-1.29]; fourth: RR, 1.16; [95% CI, 1.04-1.29]). There were no associations between neighborhood walkability and birth weight outcomes (SGA for fourth vs first quartile: RR, 1.01 [95% CI, 0.94-1.08]; LGA for fourth vs first quartile: RR, 1.06 [95% CI, 0.98-1.14]). In this population-based cross-sectional study, healthfulness of neighborhood food environments was associated with risk of SGA and LGA. The findings support use of urban design and planning guidelines to improve food environments to support healthy pregnancies and birth weight.

Continuous glucose monitoring-derived glycemic metrics and adverse pregnancy outcomes among women with gestational diabetes: a prospective cohort study

Continuous glucose monitoring (CGM) has shown potential in improving maternal and neonatal outcomes in individuals with type 1/2 diabetes, but data in gestational diabetes mellitus (GDM) is limited. We aimed to explore the relationship between CGM-derived metrics during pregnancy and pregnancy outcomes among women with GDM. We recruited 1302 pregnant women with GDM at a mean gestational age of 26.0 weeks and followed them until delivery. Participants underwent a 14-day CGM measurement upon recruitment. The primary outcome was any adverse pregnancy outcome, defined as having at least one of the outcomes: preterm birth, large-for-gestational-age (LGA) birth, fetal distress, premature rupture of membranes, and neonatal intensive care unit (NICU) admission. The individual outcomes included in the primary outcome were considered as secondary outcomes. We conducted multivariable logistic regression to evaluate the association of CGM-derived metrics with these outcomes. Per 1-SD difference in time above range (TAR), glucose area under the curve (AUC), nighttime mean blood glucose (MBG), daytime MBG, and daily MBG was associated with higher risk of any adverse pregnancy outcome, with odds ratio: 1.22 (95% CI 1.08-1.36), 1.22 (95% CI 1.09-1.37), 1.18 (95% CI 1.05-1.32), 1.21 (95% CI 1.07-1.35), and 1.22 (95% CI 1.09-1.37), respectively. Time in range, TAR, AUC, nighttime MBG, daytime MBG, daily MBG, and mean amplitude of glucose excursions were positively associated, while time blow range was inversely associated with the risk of LGA. Additionally, higher value for TAR was associated with higher risk of NICU admission. We further summarized the potential thresholds of TAR (2.5%) and daily MBG (4.8mmol/L) to distinguish individuals with and without any adverse pregnancy outcome. The CGM-derived metrics may help identify individuals at higher risk of adverse pregnancy outcomes. These CGM biomarkers could serve as potential new intervention targets to maintain a healthy pregnancy status among women with GDM. National Key R&D Program of China, National Natural Science Foundation of China, and Westlake Laboratory of Life Sciences and Biomedicine.