Risk Of Large For Gestational Age Research Articles

Association between hemoglobin A1c trajectory during pregnancy and adverse birth outcomes among non-gestational diabetic women.

Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20mmol/mol]-4.4% [25mmol/mol]), moderate-stable (range 4.6% [27mmol/mol]-5.1% [32mmol/mol]), and elevated-increasing (range 5.0% [31mmol/mol]-5.6% [38mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively. Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy.

Per- and polyfluoroalkyl substances (PFAS) and fetal growth: A nation-wide register-based study on PFAS in drinking water

BackgroundThere is inconclusive evidence for an association between per- and polyfluoroalkyl substances (PFAS) and fetal growth. ObjectivesWe conducted a nation-wide register-based cohort study to assess the associations of the estimated maternal exposure to the sum (PFAS4) of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with birthweight as well as risk of small- (SGA) and large-for-gestational-age (LGA). Materials and methodsWe included all births in Sweden during 2012–2018 of mothers residing ≥ four years prior to partus in localities served by municipal drinking water where PFAS were measured in raw and drinking water. Using a one-compartment toxicokinetic model we estimated cumulative maternal blood levels of PFAS4 during pregnancy by linking residential history, municipal PFAS water concentration and year-specific background serum PFAS concentrations in Sweden. Individual birth outcomes and covariates were obtained via register linkage. Mean values and 95 % confidence intervals (CI) of β coefficients and odds ratios (OR) were estimated by linear and logistic regressions, respectively. Quantile g-computation regression was conducted to assess the impact of PFAS4 mixture. ResultsAmong the 248,804 singleton newborns included, no overall association was observed for PFAS4 and birthweight or SGA. However, an association was seen for LGA, multivariable-adjusted OR 1.08 (95% CI: 1.01–1.16) when comparing the highest PFAS4 quartile to the lowest. These associations remained for mixture effect approach where all PFAS, except for PFOA, contributed with a positive weight. DiscussionsWe observed an association of the sum of PFAS4 – especially PFOS – with increased risk of LGA, but not with SGA or birthweight. The limitations linked to the exposure assessment still require caution in the interpretation.

Association between abnormal oral glucose tolerance test patterns in the second trimester and large for gestational age newborns

Objective: To investigate the impact of abnormal patterns of 75 g oral glucose tolerance test (OGTT) in the second trimester on the risk of large for gestational age (LGA) newborn deliveries. Methods: General clinical data and OGTT results of 66 290 pregnant women who received regular prenatal care and delivered in Guangdong Maternal and Child Health Hospital from December 24, 2016 to July 26, 2022 were collected. According to the results of OGTT, the pregnant women were divided into 8 groups: normal blood glucose group (normal fasting blood glucose, 1-hour and 2-hour after oral glucose, 54 518 cases), gestational diabetes mellitus (GDM) 0 group (only abnormal fasting blood glucose, 1 430 cases), GDM 1 group (only abnormal blood glucose at 1-hour after oral glucose, 2 150 cases), GDM 2 group (only abnormal blood glucose at 2-hour after oral glucose, 3 736 cases), GDM 0+1 group (both fasting blood glucose and 1-hour after oral glucose were abnormal, 371 cases), GDM 0+2 group (both fasting blood glucose and 2-hour after oral glucose were abnormal, 280 cases), GDM 1+2 group (abnormal blood glucose at 1-hour and 2-hour after oral glucose, 2 981 cases) and GDM 0+1+2 group (abnormal fasting blood glucose, 1-hour and 2-hour after oral glucose, 824 cases). Multivariate logistic regression was used to analyze the effects of different abnormal OGTT patterns on LGA. In addition, the blood glucose measurements at the three time points of OGTT were combined and used as continuous variables in the receiver operating characteristic (ROC) curve to evaluate the predictive value of each blood glucose measurement mode for LGA and the area under the curve (AUC) was compared. Results: (1) Multivariate logistic regression analysis showed that the risks of LGA were significantly increased in GDM 0 group (OR=1.76, 95%CI: 1.50-2.08; P<0.001), GDM 0+1 group (OR=2.29, 95%CI: 1.72-3.04; P<0.001), and GDM 0+1+2 group (OR=1.98, 95%CI: 1.61-2.43; P<0.001). (2) ROC curve analysis showed that fasting blood glucose, 1-hour after oral glucose, 2-hour after oral glucose, fasting+1-hour after oral glucose, fasting+2-hour after oral glucose, 1-hour+2-hour after oral glucose, and fasting+1-hour+2-hour after oral glucose had certain predictive value for LGA (all P<0.001). The AUC of fasting blood glucose measurement was higher than that of 2-hour blood glucose measurement in predicting LGA, and the difference was statistically significant (P<0.05). There was no significant difference in the AUC between fasting blood glucose and other blood glucose measurement modes for predicting LGA (all P>0.05). Conclusions: In the abnormal OGTT patterns, pregnant women with abnormal fasting blood glucose, abnormal fasting+1-hour after oral glucose, and abnormal fasting+1-hour+2-hour after oral glucose have an increased risk of LGA. Fasting blood glucose measurement is of great significance for the prediction of LGA, and could be used as an optimal indicator to evaluate the risk of LGA in clinical practice.

Interaction effects of MTHFR C677T and A1298C polymorphisms with maternal glycated haemoglobin levels on adverse birth outcomes.

The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p<0.05). Pregnant women with MTHFR A1298C AA or C677T CT+TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11weeks (p<0.05). For MTHFR C677T CC+TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p<0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC+TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT+TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.

Gestational Diabetes Mellitus Subtypes Classified by Oral Glucose Tolerance Test and Maternal and Perinatal Outcomes: Results of a Mexican Multicenter Prospective Cohort Study "Cuido Mi Embarazo".

This study explores the impact of gestational diabetes mellitus (GDM) subtypes classified by oral glucose tolerance test (OGTT) values on maternal and perinatal outcomes. This multicenter prospective cohort study (May 2019-December 2022) included participants from the Mexican multicenter cohort study Cuido mi Embarazo (CME). Women were classified into four groups per 75-g 2-h OGTT: 1) normal glucose tolerance (normal OGTT), 2) GDM-Sensitivity (isolated abnormal fasting or abnormal fasting in combination with 1-h or 2-h abnormal results), 3) GDM-Secretion (isolated abnormal values at 1-h or 2-h or their combination), and 4) GDM-Mixed (three abnormal values). Cesarean delivery, neonates large for gestational age (LGA), and pre-term birth rates were among the outcomes compared. Between-group comparisons were analyzed using either the t-test, chi-square test, or Fisher's exact test. Of 2,056 Mexican pregnant women in the CME cohort, 294 (14.3%) had GDM; 53.7%, 34.4%, and 11.9% were classified as GDM-Sensitivity, GDM-Secretion, and GDM-Mixed subtypes, respectively. Women with GDM were older (p = 0.0001) and more often multiparous (p = 0.119) vs without GDM. Cesarean delivery (63.3%; p = 0.02) and neonate LGA (10.7%; p = 0.078) were higher in the GDM-Mixed group than the overall GDM group (55.6% and 8.4%, respectively). Pre-term birth was more common in the GDM-Sensitivity group than in the overall GDM group (10.2% vs 8.5%, respectively; p=0.022). At 6 months postpartum, prediabetes was more frequent in the GDM-Sensitivity group than in the overall GDM group (31.6% vs 25.5%). Type 2 diabetes was more common in the GDM-Mixed group than in the overall GDM group (10.0% vs 3.3%). GDM subtypes effectively stratified maternal and perinatal risks. GDM-Mixed subtype increased the risk of cesarean delivery, LGA, and type 2 diabetes postpartum. GDM subtypes may help personalize clinical interventions and optimize maternal and perinatal outcomes.

Is large for gestational age in singletons born after frozen embryo transfer associated with freezing technique or endometrial preparation protocol? A longitudinal national French study.

Is large for gestational age (LGA) observed in babies born after frozen embryo transfer (FET) associated with either the freezing technique or the endometrial preparation protocol? Artificial cycles are associated with a higher risk of LGA, with no difference in rate between the two freezing techniques (vitrification versus slow freezing) or embryo stage (cleaved embryo versus blastocyst). Several studies have compared neonatal outcomes after fresh embryo transfer (ET) and FET and shown that FET is associated with improved neonatal outcomes, including reduced risks of preterm birth, low birthweight, and small for gestational age (SGA), when compared with fresh ET. However, these studies also revealed an increased risk of LGA after FET. The underlying pathophysiology of this increased risk remains unclear; parental infertility, laboratory procedures (including embryo culture conditions and freezing-thawing processes), and endometrial preparation treatments might be involved. A multicentre epidemiological data study was performed through a retrospective analysis of the standardized individual clinical records of the French national register of IVF from 2014 to 2018, including single deliveries resulting from fresh ET or FET that were prospectively collected in fertility centres. Complementary data were collected from the participating fertility centres and included the vitrification media and devices, and the endometrial preparation protocols. Data were collected from 35 French ART centres, leading to the inclusion of a total of 72789 fresh ET, 10602 slow-freezing FET, and 39062 vitrification FET. Main clinical outcomes were presented according to origin of the transferred embryos (fresh, slow frozen, or vitrified embryos) and endometrial preparations for FET (ovulatory or artificial cycles), comparing five different groups (fresh, slow freezing-ovulatory cycle, slow freezing-artificial cycle, vitrification-ovulatory cycle, and vitrification-artificial cycle). Foetal growth disorders were defined in live-born singletons according to gestational age and sex-specific weight percentile distribution: SGA and LGA if <10th and ≥90th percentiles, respectively. Analyses were performed using linear mixed models with the ART centres as random effect. Transfers led to, respectively, 19006, 1798, and 9195 deliveries corresponding to delivery rates per transfer of 26.1%, 17.0%, and 23.5% after fresh ET, slow-freezing FET, and vitrification FET, respectively. FET cycles were performed in either ovulatory cycles (n = 21704) or artificial cycles (n = 34237), leading to 5910 and 10322 pregnancies, respectively, and corresponding to pregnancy rates per transfer of 31.6% and 33.3%. A significantly higher rate of spontaneous miscarriage was observed in artificial cycles when compared with ovulatory cycles (33.3% versus 21.4%, P < 0.001, in slow freezing groups and 31.6% versus 21.8%, P < 0.001 in vitrification groups). Consequently, a lower delivery rate per transfer was observed in artificial cycles compared with ovulatory cycles both in slow freezing and vitrification groups (15.5% versus 18.9%, P < 0.001 and 22.8% versus 24.9%, P < 0.001, respectively). Among a total of 26585 live-born singletons, 16413 babies were born from fresh ET, 1644 from slow-freezing FET, and 8528 from vitrification FET. Birthweight was significantly higher in the FET groups than in 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 with the fresh ET group whatever the method used for embryo freezing. In a multivariable analysis, the risk of LGA following FET was significantly increased in artificial compared with ovulatory cycles. In contrast, the risk of LGA was not associated with either the freezing procedure (vitrification versus slow freezing) or the embryo stage (cleaved embryo versus blastocyst) at freezing. Regarding the vitrification method, the risk of LGA was not associated with either the vitrification medium used or the embryo stage. No data were available on maternal context, such as parity, BMI, infertility cause, or maternal comorbidities, in the French national database. In particular, we cannot exclude that the increased risk of LGA observed following FET with artificial cycles may, at least partially, be associated with a confounding effect of some maternal factors. No information about embryo culture and incubation conditions was available. Most of the vitrification techniques were performed using the same device and with two main vitrification media, limiting the validity of a comparison of risk for LGA according to the device or vitrification media used. Our results seem reassuring, since no potential foetal growth disorders following embryo vitrification in comparison with slow freezing were observed. Even if other factors are involved, the endometrial preparation treatment seems to have the greatest impact on LGA risk following FET. FET during ovulatory cycles could minimize the risk for foetal growth disorders. This work has received funding from the French Biomedicine Agency (Grant number: 19AMP002). None of the authors has any conflict of interest to declare. N/A.

Perinatal outcomes of frozen-thawed embryo transfer following blastocyst-stage embryo transfer compared to those of cleavage-stage embryo transfer: Analysis of 9,408 singleton newborns using propensity score analysis

Objective: Regarding frozen-thawed embryo transfer (FET), there is limited consensus on whether extending embryo culture from the cleavage stage to the blastocyst stage affects perinatal outcomes. This study aimed to compare perinatal outcomes of singletons between blastocyst-stage transfer (BT) and cleavage-stage transfer (CT) in FET. Methods: A total of 9,408 FET cycles that met the inclusion criteria were included in this retrospective cohort study between 2019 and 2022. Blastocyst-stage embryo transfers were performed in the BT group, and cleavage-stage embryo transfers were performed in the CT group. Multivariate logistic regression analyses were performed, as well as propensity score matching (PSM) to adjust for confounders. Results: After PSM, a higher risk of preterm birth (PTB) (OR 1.23, 95% CI 1.00–1.50, P=0.048) and being large for gestational age (LGA) (OR 1.16, 95% CI 1.00–1.35, P=0.050) was observed in the BT group compared to that in the CT group. After stratified PSM, in the subgroup under 35 years of age, only an increased risk of LGA was observed in the BT group compared to the CT group. Perinatal outcomes in the double-embryo transfer subgroup were similar to those in the unstratified group. However, in the subgroup beyond 35 years of age and the single-embryo transfer subgroup, perinatal outcomes were not statistically different between the BT and CT groups (P&gt;0.05). Conclusions: In FET, prolonged embryo culture to the blastocyst stage increased the risk of PTB and LGA in single fetuses. However, stratified analysis based on age and the number of transferred embryos yielded different results, necessitating further mechanistic studies.

The association between gestational weight trajectories in women with gestational diabetes and their offspring's weight from birth to 40 months

AimsTo identify the gestational weight gain (GWG) patterns in women with gestational diabetes mellitus (GDM) and evaluate their association with offspring weight status from birth to 40 months.Materials and methodsThis study included 2,723 GDM-mother–child pairs from the Beijing Birth Cohort Study. The association between GWG trajectories identified by the latent class model and offspring weight outcomes from birth to 40 months were evaluated, after adjustment for maternal age, parity, pre-pregnancy body mass index, maternal height, and blood glucose levels.ResultsThree GWG rate groups, including the non-excessive GWG group (1,994/2,732), excessive GWG group (598 /2,732), and excessive early GWG group (140/2,732), were identified in women with GDM, respectively. Compared to the non-excessive GWG group, the adjusted OR (aOR) and 95% CI were 1.83 (1.35–2.47) and 1.79 (1.06–3.01) for macrosomia, 1.33 (1.07–1.66) and 1.48 (1.01–2.17) for large for gestational age (LGA) in the excessive GWG group and excessive early GWG group. Excessive GWG was also associated with an increased risk of BMI-for-age at 40 months (aOR = 1.66, 95% CI 1.14–2.42).ConclusionsBoth excessive GWG and excessive early GWG increased the risk of macrosomia and LGA in women with GDM, but only the excessive GWG was associated with childhood overweight/obesity. The results suggest the long-term impact of GWG on offspring weight status in women with GDM and the potential benefits of GWG restriction after GDM diagnosis.

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.

Continuous glucose monitoring in pregnancies with type 1 diabetes: small increases in time-in-range improve maternal and perinatal outcomes

BackgroundContinuous glucose monitors (CGM) provide detailed information regarding glycemic control in pregnant patients with type 1 diabetes (T1D). Little data have been published examining the association between CGM parameters and perinatal outcomes among gravidas with T1D using CGM. ObjectiveTo examine the association between perinatal outcomes and time-in-range (TIR) as assessed by CGM used in pregnant individuals with T1D. We hypothesized that higher TIR would be associated with lower risk of adverse perinatal outcomes. Study designThis multicenter retrospective cohort study included all gravidas with T1D using CGM who delivered in 2020-2022 at 5 University of California sites. Only those with CGM target range set to 70-140 mg/dL (±10 mg/dL) were included. TIR (%) was recorded at 12, 16, 20, 24, 28, and 32 weeks. The primary maternal and neonatal outcomes were preeclampsia and large for gestational age (LGA), defined as birthweight (BW) ≥ 95th percentile. Kruskal-Wallis tests were used to compared median TIR in those with and without the primary outcomes. Log-binomial regression was used to obtain risk ratios, with adjustment for microvascular disease and years with T1D. ResultsA total of 91 patients were included. Most used an insulin pump (81%) and did not have diabetic microvascular disease (72%). Median time since diagnosis of T1D was 16 years, and median periconception A1c was 6.7%. Compared to those with preeclampsia, normotensive gravidas had significantly higher TIR at nearly every time point. A similar pattern was seen for those with normal BW infants compared to LGA infants. On adjusted analyses, every 5-unit increase in TIR at 12 weeks was associated with a 45% and 46% reduction in the risk of preeclampsia and LGA, respectively (ARR 0.55, 95% CI 0.30-0.99 for preeclampsia; ARR 0.54, 95% CI 0.29-0.99 for LGA). ConclusionsHigher TIR is associated with lower risk of preeclampsia and LGA. This association is seen early in gestation, when each 5-unit increase in TIR is associated with ∼50% reduction in the risk of these complications. These findings can be used to counsel patients regarding risk of pregnancy complications at specific TIR values and to encourage patients that even small improvements in TIR can have significant impact on pregnancy outcomes. Larger studies are needed to further explore these findings and to identify optimal TIR to reduce perinatal complication rates.

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.