Large For Gestational Age Rates Research Articles

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.

Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

Diabetes Group Prenatal Care: A Systematic Review and Meta-analysis.

To estimate the effect of diabetes group prenatal care on rates of preterm birth and large for gestational age (LGA) among patients with diabetes in pregnancy compared with individual diabetes prenatal care. We searched Ovid Medline (1946-), Embase.com (1947-), Scopus (1823-), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. We searched electronic databases for randomized controlled trials (RCTs) and observational studies comparing diabetes group prenatal care with individual care among patients with type 2 diabetes mellitus or gestational diabetes mellitus (GDM). The primary outcomes were preterm birth before 37 weeks of gestation and LGA (birth weight at or above the 90th percentile). Secondary outcomes were small for gestational age, cesarean delivery, neonatal hypoglycemia, neonatal intensive care unit admission, breastfeeding at hospital discharge, long-acting reversible contraception (LARC) uptake, and 6-week postpartum visit attendance. Secondary outcomes, limited to the subgroup of patients with GDM, included rates of GDM requiring diabetes medication (A2GDM) and completion of postpartum oral glucose tolerance testing (OGTT). Heterogeneity was assessed with the Cochran Q test and I2 statistic. Random-effects models were used to calculate pooled relative risks (RRs) and weighted mean differences. Eight studies met study criteria and were included in the final analysis: three RCTs and five observational studies. A total of 1,701 patients were included in the pooled studies: 770 (45.3%) in diabetes group prenatal care and 931 (54.7%) in individual care. Patients in diabetes group prenatal care had similar rates of preterm birth compared with patients in individual care (seven studies: pooled rates 9.5% diabetes group prenatal care vs 11.5% individual care, pooled RR 0.77, 95% CI, 0.59-1.01), which held for RCTs and observational studies. There was no difference between diabetes group prenatal care and individual care in rates of LGA overall (four studies: pooled rate 16.7% diabetes group prenatal care vs 20.2% individual care, pooled RR 0.93, 95% CI, 0.59-1.45) or by study type. Rates of other secondary outcomes were similar between diabetes group prenatal care and individual care, except patients in diabetes group prenatal care were more likely to receive postpartum LARC (three studies: pooled rates 46.1% diabetes group prenatal care vs 34.1% individual care, pooled RR 1.44, 95% CI, 1.09-1.91). When analysis was limited to patients with GDM, there were no differences in rates of A2GDM or postpartum visit attendance, but patients in diabetes group prenatal care were significantly more likely to complete postpartum OGTT (five studies: pooled rate 74.0% diabetes group prenatal care vs 49.4% individual care, pooled RR 1.58, 95% CI, 1.19-2.09). Patients with type 2 diabetes and GDM who participate in diabetes group prenatal care have similar rates of preterm birth, LGA, and other pregnancy outcomes compared with those who participate in individual care; however, they are significantly more likely to receive postpartum LARC, and those with GDM are more likely to return for postpartum OGTT. PROSPERO, CRD42021279233.

Impact of a modified screening approach during the COVID-19 pandemic on the diagnosis and outcomes of gestational diabetes mellitus: A population-level analysis of 90,518 pregnant women.

To provide real-world evidence on the uptake of and outcomes associated with the modified gestational diabetes mellitus (GDM) screening approach offered during the COVID-19 pandemic compared with the standard screening approach. All pregnancies between 01 January 2020 and 31 December 2021, in Alberta, Canada, were included in the study. We examined GDM screening and diagnosis rates, and large-for-gestational-age (LGA) outcomes. Annual GDM screening rates were > 95% during the study time period. Overall, 84.7%, and 11.6% of the 92,505 pregnancies underwent standard and modified screening for GDM, respectively. The use of modified screening was the highest among deliveries in August 2020 (49.8%) which corresponded to the early first wave of the pandemic. GDM diagnosis rate was lower in the modified screening (7.4%) than in the standard screening (12.3%, p < 0.001) group. The LGA rates in the modified screening with GDM and the standard screening with GDM groups were 24.8% and 12.6%, respectively (p < 0.001). Women in the modified screening with GDM group were at a higher risk of having an LGA infant (adjusted odds ratio: 3.46; 95% confidence interval: 2.93, 4.08) compared to the standard screening with no GDM group. The COVID-19 epidemic had no impact on screening for GDM. Women who underwent modified screening, based on HbA1c/random plasma glucose, had lower rates of GDM cases.

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

Prevalence of gestational diabetes mellitus, maternal obesity and associated perinatal outcomes over 10 years in an Australian tertiary maternity provider

BackgroundThe International Association of Diabetes in Pregnancy Study Groups (IADPSG) gestational diabetes mellitus (GDM) criteria have been heavily scrutinised with concerns that the consequent GDM prevalence increase has not been associated with improved perinatal outcomes. AimsAt a tertiary hospital in Melbourne, Australia we aimed to evaluate prevalence trends for GDM, type 2 diabetes (T2DM), maternal obesity and large-for-gestational age (LGA) and assess changes in perinatal outcomes following IADPSG criteria uptake in 2015. MethodsA retrospective cohort study of singleton births from 20 weeks’ gestation was conducted between 1st January 2011 and 31st December 2020. Maternal characteristics and perinatal outcomes were extracted from medical records. Results52,795 pregnancies were included. GDM prevalence increased 2.7 times from 8.9% in 2011 to 23.7% in 2020 and increased annually by 8.59% (95%CI 7.77, 9.42). The rate of T2DM increased annually by 11.69% (95%CI 7.72, 16.67). Obesity prevalence increased annually by 3.18% (95%CI 2.58, 3.78). Induction of labour (IOL) prevalence increased annually by 8.35% (95%CI 5.69, 11.06). LGA prevalence remained unchanged. Increasing maternal obesity was the major contributing factor for LGA prevalence. ConclusionsFrom 2011 to 2020 GDM, obesity and T2DM prevalence increased significantly, with associated increased IOL, without change in LGA rates. Prospective studies are required to explore interactions between GDM, obesity, LGA and obstetric interventions.

Exploring the Optimal Diagnostic Thresholds of Hyperglycemia During Pregnancy

Exploring the Optimal Diagnostic Thresholds of Hyperglycemia During Pregnancy

Risk of obstetric and neonatal morbidity in gestational diabetes in a single institution: A retrospective, observational study.

Gestational diabetes mellitus (GDM) is defined as a carbohydrate intolerance with onset or first recognition occurring during pregnancy and GDM could be risk factor for various maternal fetal complications. This study aimed to investigate risks of maternal and neonatal outcomes according to GDM and normal glucose tolerance. This retrospective, observational study included singleton pregnant women who had received a 50-g oral glucose challenge test in 2nd trimester of gestation and gave birth at National Health Insurance Service Ilsan Hospital. Maternal and neonatal complications were compared between GDM and non-GDM groups. Among the 682 women, 56 were diagnosed with GDM and 626 were non-GDM group. Maternal age was older and prepregnant body mass index was higher in GDM. The rate of cesarean delivery, preeclampsia, and transfusion was similar; however, the incidence of preterm birth was higher in GDM. Multivariate analysis, however, showed that GDM was independent risk factor only for preterm birth in <37 weeks (adjusted odds ratio, 2.25; 95% confidence interval, 1.16–4.36). Regarding neonatal morbidities, APGAR score <7 at 5 minutes and the rate of macrosomia were similar; however, the rates of neonatal intensive care unit (NICU) admission, large for gestational age (LGA), and intubation were higher in GDM. Multivariate analysis, however, showed that GDM was not independent risk factor for LGA, NICU admission, and intubation rate. Compared with the non-GDM group, GDM was associated with an increased likelihood of preterm birth <37 weeks, however, did not increase cesarean delivery, postpartum hemorrhage, LGA, and NICU admission rate. This study showed that the majority of women with GDM delivered with similar maternal and neonatal outcomes in non-GDM women.

Factors associated with large-for-gestational-age infants born after frozen embryo transfer cycles

To examine trends of frozen embryo transfer (FET) proportions and large-for-gestational-age (LGA) incidence and determine risk factors for LGA infants after FET. Retrospective cohort study. Not applicable. Frozen embryo transfer cycles. None. Singleton LGA infant. The percentage of FETs increased from 20%-74% of transfers, whereas the rate of LGA among FET singleton births decreased from 18%-12% during 2004-2018. In a subanalysis of 127,525 FET-associated singleton live births during 2016-2018, patient factors associated with LGA were higher-than-normal maternal body mass index (body mass index [BMI], 25.0-29.9 kg/m2; adjusted relative risk [aRR], 1.31; 95% confidence interval [CI], 1.26-1.36; BMI, 30.0-34.9 kg/m2; aRR, 1.48; 95% CI, 1.41-1.55; and BMI, >35 Kg/m2; aRR, 1.68; 95% CI, 1.59-1.77) and ≥1 prior birth vs. none. Low maternal BMI (<18.5 vs. 18.5-24.9 kg/m2) and cycles involving patients who were non-Hispanic (NH) Asian/Native Hawaiian/Pacific Islander, NH Black, or Hispanic (compared with NH White) were at lower risk of LGA infants. Cycle factors associated with LGA included gestational carrier use (aRR, 1.25; 95% CI, 1.16-1.34) and donor sperm (aRR, 1.17; 95% CI, 1.10-1.25). Although the number and proportion of FET cycles increased from 2004-2018, the rate of LGA after FET decreased. Maternal BMI, parity, and race/ethnicity were the strongest risk factors for LGA infants after FET.

Impaired Fasting Glucose in Pregnancy: Improved Perinatal Outcomes with Active Glycemic Management.

This study aimed to assess the association between active glycemic management and large for gestational age (LGA) neonates and cesarean delivery (CD) among pregnant women with impaired fasting glucose (IFG). Retrospective cohort study using electronic health record data of women with IFG who delivered at the Kaiser Permanente Northern California from 2012 to 2017. IFG was defined as isolated fasting glucose ≥95 mg/dL. Women with gestational diabetes mellitus (GDM) or in whom GDM could not be ruled out were excluded. Baseline and treatment characteristics, and pregnancy outcomes were compared among women with IFG who participated in telephonic home glucose monitoring and glycemic management through a centralized standardized program (participants) with those who did not participate (nonparticipants). The relative risks (RRs) of perinatal complications associated with participation versus nonparticipation were estimated with Poisson's regression models. We identified 1,584 women meeting inclusion criteria of whom 1,151 (72.7%) were participants and 433 (27.3%) were nonparticipants. There were no differences between groups in baseline characteristics or comorbidities, except for higher mean levels of fasting glucose (FG) at the time of IFG diagnosis in participants than in nonparticipants (98.9 vs. 98.0 mg/dL, p = 0.01). Participants received hypoglycemic medications more frequently than nonparticipants (68.2 vs. 0.9%, p < 0.01). The rate of LGA was significantly lower in participants compared with nonparticipants (19.1 vs. 25.0%, p = 0.01). After adjusting for age, race/ethnicity, education, body mass index, and level of FG impairment, the RR for LGA for participants compared with nonparticipants was 0.68, 95% CI: 0.55-0.84. The risk of CD did not differ significantly by participation status, in unadjusted or adjusted analyses. Active standardized glycemic management was associated with a decreased risk of LGA for women with IFG. This finding supports an active glycemic management strategy for patients with IFG during pregnancy to reduce the risk of LGA, similar to GDM management. · Pregnant women with IFG have increased rates of LGA.. · Active management of IFG is associated with a decreased LGA.. · Treatment of IFG like GDM may improve perinatal outcomes..

Association between Trimester-Specific Gestational Weight Gain Rate and Maternal and Neonatal Outcomes

Background: To investigate the associations of adjusting gestational weight gain rate (GWGr) with maternal and neonatal outcomes. Methods: We analyzed 6235 singleton pregnancies among women with normal pre-pregnancy body mass index at two medical centers in China during 2016~2018 to figure out whether pregnancy outcomes could be improved by adjusting GWGr timely when the first-trimester weight gain rate (GWGr-1) and/or the second-trimester weight gain rate (GWGr-2) were inappropriate. Results: When GWGr-1 was excessive, excessive GWGr during the second and third trimesters of pregnancy (late GWGr) was associated with a higher risk of cesarean section (CS), postpartum hemorrhage (PPH), obstructed and prolonged labor and large for gestational age (LGA), and inadequate late GWGr was associated with a lower prevalence of CS and hypertensive disorders of pregnancy (HDP). In pregnancies with inadequate GWGr-1, excessive late GWGr was related to a higher rate of CS, LGA and HDP. Among women with adequate GWGr-1, excessive GWGr in the third trimester (GWGr-3) was positively associated with CS, HDP, and obstruction and prolongation of labor if their GWGr-2 was excessive, and excessive GWGr-3 was associated with a higher risk of CS even though tFheir GWGr-2 was inadequate. Conclusions: Prompt control of GWGr, even during late pregnancy, was beneficial to improving pregnancy outcomes.

Greater estimated fetal weight and birth weight in IVF/ICSI pregnancy after frozen-thawed vs fresh blastocyst transfer: prospective cohort study with novel unified modeling methodology.

To compare, using a unified approach, standardized estimated fetal weight (EFW) trajectories from the second trimester to birth and birth-weight (BW) measurements in in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies obtained after frozen-thawed vs fresh blastocyst transfer (BT). This was a secondary analysis of a prospective longitudinal cohort study performed at the Fetal Medicine and Obstetric Departments of San Raffaele Hospital in Milan, Italy, from January 2016 to December 2020. Eligible for inclusion were singleton viable gestations conceived by autologous IVF/ICSI conception after fresh or frozen-thawed BT that underwent standard fetal biometry assessment at 19-41 weeks and had BW measurements available. All ultrasound assessments were performed by operators blinded to the employment of cryopreservation. Patients with twin gestation, significant pregestational disease, miscarriage, major fetal abnormalities and use of other types of medically assisted reproduction techniques were excluded. EFW and BW Z-scores and their trajectories were analyzed using general linear models (GLM) and logistic regression with a unified modeling methodology based on the Fetal Medicine Foundation fetal and neonatal population weight charts, adjusting for major confounders. Differences between prenatal EFW and postnatal BW centiles in the two groups were assessed and compared using contingency tables, χ2 test and conversion of prenatal to postnatal centiles. A total of 631 IVF/ICSI pregnancies were considered, comprising 263 conceived following fresh BT and 368 after frozen-thawed BT. A total of 1795 EFW observations were available (n = 715 in fresh BT group and n = 1080 in frozen-thawed BT group; median of three observations per patient). EFW and BW < 10th centile were significantly more frequent in the fresh than in the frozen-thawed BT group (P = 0.003 and P < 0.001, respectively). EFW and BW > 90th centile were significantly more frequent in the frozen-thawed vs fresh BT group (P = 0.034 and P = 0.002, respectively). GLM showed significantly decreasing EFW Z-scores with advancing gestational age (GA) in both groups. The effect of GA was assumed to be equal in the two study groups, as no significant interaction effect was found. Smoothed mean EFW Z-scores from 19 weeks of gestation to term and smoothed mean BW Z-scores were both significantly higher in the frozen-thawed compared with the fresh BT group (EFW Z-score, 0.70 ± 1.29 vs 0.28 ± 1.43; P < 0.001; BW Z-score, 0.04 ± 1.08 vs -0.31 ± 1.28; P < 0.001). Mean smoothed EFW Z-score values in the frozen-thawed vs fresh BT groups were 1.01 ± 0.12 vs 0.60 ± 0.08 at 19-27 weeks, 0.36 ± 0.07 vs -0.06 ± 0.04 at 28-35 weeks and -0.66 ± 0.01 vs -0.88 ± 0.02 at 36-41 weeks. Mean smoothed BW Z-score values in the frozen-thawed vs fresh BT groups were -0.80 ± 0.14 vs -1.20 ± 0.10 at 28-35 weeks and 0.22 ± 0.16 vs -0.24 ± 0.14 at 36-41 weeks. Assessment of EFW and BW concordance showed a significantly greater rate of postnatal confirmation of prenatally predicted small-for-gestational age (SGA) < 10th centile in the fresh compared with the frozen-thawed BT group (P < 0.001), whereas the rate of postnatal confirmation of large-for-gestational age (LGA) > 90th centile was significantly higher in the frozen-thawed vs the fresh BT group (P < 0.001). Logistic regression analysis showed that the smoothed rate of EFW < 3rd centile was about 6-fold higher in the fresh vs frozen-thawed BT group (P < 0.001), whereas the smoothed rates of EFW 90th -97th centile and > 97th centile were nearly double in the frozen-thawed compared with the fresh BT group (P < 0.05 and P < 0.001, respectively). Robust novel unified prenatal-postnatal modeling in IVF/ICSI pregnancies after frozen-thawed or fresh BT from 19 weeks of gestation to birth showed non-divergent growth trajectories, with higher EFW and BW Z-scores in the frozen-thawed vs fresh BT group. The mean EFW Z-scores in both IVF/ICSI groups were greater than those expected for natural conceptions, being highest in the midtrimester and decreasing with advancing gestation in both groups, becoming negative after 32 weeks in the fresh and after 35 weeks in the frozen-thawed BT group. Mean BW Z-scores were negative in both groups, with lower values in preterm fetuses, and increased with advancing gestation, becoming positive at term in the frozen-thawed BT group. IVF/ICSI conceptions from frozen-thawed as compared to fresh BT presented increased rate of LGA and reduced rate of SGA both prenatally and postnatally. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Trends in maternal characteristics and perinatal outcomes among Japanese pregnant women with type 1 and type 2 diabetes from 1982 to 2020.

Aims/IntroductionThis study investigated the time trends of the maternal characteristics and perinatal outcomes of Japanese pregnant women with diabetes.Materials and MethodsThis retrospective study included 621 deliveries in 429 Japanese women with diabetes between 1982 and 2020. The association of the delivery date with clinical features was analyzed using the generalized estimating equations to adjust for the within‐person correlation.ResultsThe mean age of delivery and the mean diabetes duration increased over time (both P < 0.001), while the prevalence of diabetic retinopathy decreased (P = 0.006). The mean HbA1c values during pregnancy decreased significantly over time (all P < 0.001). The decreasing trends were associated with preterm delivery (P = 0.021) but not with other perinatal outcomes. The time trends were significantly different between patients with type 1 diabetes mellitus and with type 2 diabetes mellitus in large for gestational age (LGA) and stillbirth (both P for interaction <0.05). The rate of LGA decreased among patients with type 2 diabetes (P = 0.003) but not those with type 1 diabetes (P = 0.413). In contrast, the prevalence of stillbirth was decreased among those with type 1 diabetes (P < 0.001) but not those with type 2 diabetes (P = 0.768). The proportion of major congenital anomalies did not change in the overall population (P = 0.259) and among patients with type 2 diabetes (P = 0.229), but it increased among those with type 1 diabetes (P = 0.044), although the difference between those with type 1 diabetes and type 2 diabetes was not statistically significant (P for interaction = 0.166).ConclusionsMaternal glycemic control has improved over the decades, whereas the improvement of perinatal outcomes has been limited. Perinatal outcomes still need to be improved in Japanese women with diabetes.

Trends and burden of diabetes in pregnancy among Aboriginal and non-Aboriginal mothers in Western Australia, 1998\u20132015

BackgroundDiabetes in pregnancy (DIP), which includes pre-gestational and gestational diabetes, is more prevalent among Aboriginal women. DIP and its adverse neonatal outcomes are associated with diabetes and cardiovascular disease in the offspring. This study investigated the impact of DIP on trends of large for gestational age (LGA) in Aboriginal and non-Aboriginal populations, and added to the limited evidence on temporal trends of DIP burden in these populations.MethodsWe conducted a retrospective cohort study that included all births in Western Australia between 1998 and 2015 using linked population health datasets. Time trends of age-standardised and crude rates of pre-gestational and gestational diabetes were estimated in Aboriginal and non-Aboriginal mothers. Mixed-effects multivariable logistic regression was used to estimate the association between DIP and population LGA trends over time.ResultsOver the study period, there were 526,319 births in Western Australia, of which 6.4% were to Aboriginal mothers. The age-standardised annual rates of pre-gestational diabetes among Aboriginal mothers rose from 4.3% in 1998 to 5.4% in 2015 and remained below 1% in non-Aboriginal women. The comparable rates for gestational diabetes increased from 6.7 to 11.5% over the study period in Aboriginal women, and from 3.5 to 10.2% among non-Aboriginal mothers. LGA rates in Aboriginal babies remained high with inconsistent and no improvement in pregnancies complicated by gestational diabetes and pre-gestational diabetes, respectively. Regression analyses showed that DIP explained a large part of the increasing LGA rates over time in Aboriginal babies.ConclusionsThere has been a substantial increase in the burden of pre-gestational diabetes (Aboriginal women) and gestational diabetes (Aboriginal and non-Aboriginal) in recent decades. DIP appears to substantially contribute to increasing trends in LGA among Aboriginal babies.

Association between maternal glucose and large for gestational outcomes: Real-world evidence to support Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study findings.

To compare large for gestational age (LGA) rates by maternal glucose levels in a real-world setting with those in the Hyperglycaemia and Adverse Pregnancy Outcomes (HAPO) study. To examine the association between fasting plasma glucose (FPG), 1- and 2-h on a 75-g oral glucose tolerance tests (OGTT) and LGA. Pregnancies were categorized according to HAPO thresholds. Category-specific LGA rates were compared to those in HAPO. Categories with glucose thresholds below or above the diagnostic criteria for gestational diabetes mellitus (GDM) were labelled as lower and higher/GDM, respectively. GDM pregnancies were further stratified according to FPG or post-load elevations and logistic regression was used to examine their independent association with LGA. In our cohort of 97,032 pregnancies, rates of LGA increased with increasing maternal glucose in lower categories of FPG, 1- and 2-h glucose (trend p<0.01). However, LGA rates in higher/GDM categories were significantly lower in our study than those in HAPO for 1- and 2-h glucose, but not for FPG. Elevated FPG alone was associated with an almost twofold increase in risk of LGA, while elevated post-load glucose alone was associated with a 20% reduction in risk of LGA, compared to negative OGTT. Real-world data confirm the HAPO study findings at lower levels of maternal glycaemia. At higher levels, GDM diagnosis and treatment appear to be effective in reducing rates of LGA in pregnancies with post-load glucose elevations, but not elevated FPG. Elevated FPG is a stronger predictor of LGA than post-load glucose elevations.

Increased abdominal circumference as predictor of macrosomia without evidence of adverse obstetrical or neonatal outcomes

Ultrasound is used as a screening tool for suspected fetal macrosomia, primarily focused on estimated fetal weight (EFW). The interpretation of isolated increased abdominal circumference (AC), however, is unclear. We aimed to determine if increased AC alone, in the setting of normal EFW and the absence of diabetes, is associated with any adverse obstetric or neonatal outcomes. This is a secondary analysis of a prospective observational study of individuals with negative diabetes screening between 2016-2020. Third trimester ultrasound data was examined to develop our study group (AC ≥ 95%tile, EFW< 95%tile) and comparison group (AC< 95%tile, EFW< 95%tile). Obstetric (induction, shoulder dystocia, primary Cesarean rate, postpartum hemorrhage) and neonatal (large for gestational age (LGA) phototherapy, hypoglycemia, NICU admission) outcomes were compared using chi-square analyses. We performed logistic regression to evaluate which antepartum factors may be most predictive of AC ≥ 95%tile and created ROC curves with gestational weight gain (up to 28weeks) and glucose tolerance testing (GTT). A total of 1239 individuals were included in the study population. Those with AC ≥ 95%tile (n = 40) had an increased rate of LGA (17% vs 2.4%, p< 0.001). There were no differences between rates of induction, shoulder dystocia, primary Cesarean, postpartum hemorrhage, phototherapy, neonatal hypoglycemia, or NICU admission (Table 1). Using logistic regression, weight gain and GTT values were found to be significant in predicting AC ≥ 95%tile. ROC curves were developed, the better model being GTT (AUC 0.637), suggesting a 1 hour GTT > 105 may be predictive of AC ≥ 95%tile (Figure 1). AC ≥ 95%tile was associated with macrosomia, but not with other adverse obstetric/neonatal outcomes. Additionally, a 1 hour GTT > 105, while normal, seems to be a risk factor for AC ≥ 95%tile and should be considered indication for a third trimester growth scan. Further studies are needed to determine if antepartum surveillance should be recommended in this population.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Elevated Anti-Müllerian Hormone Is an Independent Risk Factor for Preterm Birth Among Patients With Overweight Polycystic Ovary Syndrome.

ObjectiveTo explore whether elevated anti-Müllerian hormone (AMH) levels affect the rate of preterm birth (PTB) among PCOS patients with different BMIs.MethodsIn this retrospective cohort study, patients with PCOS who had undergone IVF/ICSI from January 2017 to December 2019 were included for potential evaluation. A total of 2368 singleton live births from PCOS patients were included. According to the BMI, all the PCOS patients were divided into two groups: BMI<24 kg/m2 and BMI≥24 kg/m2. In total, 1339 PCOS patients with a BMI<24 kg/m2 were grouped according to their serum AMH levels: ① <2.71 ng/ml (n=333), ② 2.71-4.08 ng/ml (n=330), ③ 4.09-6.45 ng/ml (n=351), and ④ >6.45 ng/ml (n=325). Additionally, 1029 cycles of patients with a BMI≥24 kg/m2 were grouped according to the serum AMH level: ① <2.71 ng/ml (n=255), ② 2.71-4.08 ng/ml (n=267), ③ 4.09-6.45 ng/ml (n=239), and ④ >6.45 ng/ml (n=268), with <2.71 ng/ml being considered the reference group. The grouping was based mainly on the interquartile range of serum AMH levels. The primary outcome of the study was PTB. The secondary outcomes were low birth weight (LBW), small for gestational age (SGA), macrosomia and large for gestational age (LGA).ResultsRegarding PCOS patients with a BMI<24 kg/m2, compared with the PTB rate of the AMH <2.71 ng/ml group, the PTB rates of the different groups were not significantly different (AMH 2.71-4.08, AOR (95% CI)=1.01 (0.52-2.00), P=0.99; AMH 4.09-6.45, AOR (95% CI)=0.93 (0.45-1.91), P=0.85; AMH>6.45, AOR (95% CI)=0.78 (0.35-1.73), P=0.54). Regarding PCOS patients with a BMI ≥24 kg/m2, compared with the PTB rate of the AMH <2.71 ng/ml group, the PTB rate of the AMH>6.45 ng/ml group was significantly higher (OR=2.47; 95% CI=1.34-4.55). After multiple logistic regression analysis, the risk of PTB in the AMH>6.45 ng/ml group was 2.1 times that in the AMH<2.71 ng/ml group (AOR=2.1, 95% CI=1.01-4.37, P=0.04). However, no statistically significant difference was found in the rate of SGA, LBW, macrosomia or LGA among patients in the different serum AMH groups.ConclusionFor PCOS patients, a BMI≥24 kg/m2 plus serum AMH>6.45 ng/ml (75th percentile) is an independent risk factor for PTB.

Early-Pregnancy Intermediate Hyperglycemia and Adverse Pregnancy Outcomes Among Women Without Gestational Diabetes

ContextUniversal early-pregnancy screening for overt diabetes reveals intermediate hyperglycemia (fasting plasma glucose [FPG] [5.1-6.9 mM]).ObjectiveWe evaluated the association between early-pregnancy intermediate hyperglycemia and adverse pregnancy outcomes among women without gestational diabetes.MethodsThis retrospective cohort study was conducted at the Obstetrics and Gynecology Hospital, Shanghai, China, from 2013 to 2017. All singleton pregnancies with FPG less than or equal to 6.9 mM in early pregnancy and receiving a 75-g oral glucose tolerance test (OGTT) were included. Women with prepregnancy diabetes were excluded. Individuals with normal OGTT were analyzed. Pregnancy outcomes for FPG less than 5.1 mM and intermediate hyperglycemia were evaluated. The primary outcomes were large for gestational age (LGA) and primary cesarean delivery. Multivariate logistic regressions were conducted. Statistical significance was defined as P less than .05.ResultsIn total, 24 479 deliveries were included, of which 23 450 (95.8%) had normal OGTTs later in pregnancy (NGT). There were 807 (3.4%) women who had an FPG of 5.1 to 6.9 mM in early pregnancy. Compared to the NGT group with an FPG of less than 5.1 mM in early pregnancy (N = 20692), the intermediate hyperglycemia NGT group (N = 693) had a higher age and body mass index (BMI), and significantly higher rates of LGA, primary cesarean delivery, preterm birth, preeclampsia, and neonatal distress. The rates of primary cesarean delivery (adjusted odds ratio [AOR] 1.24; 95% CI, 1.05-1.45), preterm birth (AOR 1.75; 95% CI, 1.29-2.36), and neonatal distress (AOR 3.29; 95% CI, 1.57-6.89) remained statistically significantly higher after adjustments for maternal age, BMI, and other potential confounding factors.ConclusionWomen with intermediate hyperglycemia in early pregnancy are at an increased risk for adverse maternal-fetal outcomes, even with normal future OGTTs.

Association Between HbA1c Levels on Adverse Pregnancy Outcomes During Pregnancy in Patients With Type 1 Diabetes.

ContextDespite optimization of metabolic balance during pregnancy in type 1 diabetes (T1D), maternal–fetal complications remain higher than in the background population.ObjectiveWe examined whether there is an association between glycated hemoglobin (HbA1c) levels and these complications.MethodsRetrospective study of pregnancies in 678 T1D subjects at Lille Hospital (1997-2019). The association between variations in HbA1c levels and complications was examined. The composite criterion (CC) was defined as having at least 1 of the following complications: prematurity, pre-eclampsia, large for gestational age (LGA), small for gestational age (SGA), or cesarean section.ResultsAmong the 678 births, median preconception HbA1c was 7.2% (55 mmol/mol), 361 were LGA (56%), 29 were SGA (4.5%), and 504 were births without preterm delivery (76.1%). The CC occurred in 81.8%. Higher HbA1c during the first trimester was associated with the CC (OR 1.04; 95% CI 1.02-1.06 per 0.1% increase; P < .001). Higher HbA1c during the third trimester was associated with the CC (OR 1.07; 95% CI 1.03-1.10 per 0.1% increase; P < .001). The group defined by a first trimester Hba1c >6.5% (48 mmol/mol) and a third trimester HbA1c <6% was associated with an increased rate of the CC (OR 2.81; 95% CI 1.01-7.86) and an increased rate of LGA (OR 2.20; 95% CI 1.01- 4.78).ConclusionElevated HbA1c is associated with maternal–fetal complications. Despite optimization of metabolic balance during the third trimester, for patients with early glycemic imbalance the risk of LGA persists.

Associations between aspirin prophylaxis and fetal growth and preeclampsia in women with pregestational diabetes.

Current guidelines recommend low-dose aspirin for preeclampsia prophylaxis in all women with pregestational (type one and type two) diabetes mellitus. Most trials showing the efficacy of low-dose aspirin in reducing preeclampsia risk have either excluded or included only small numbers of such women. To evaluate the association of low-dose aspirin prophylaxis in women with pregestational diabetes with the incidence of large for gestational age (LGA) infants and preeclampsia. A retrospective observational study of pregnancies to women with pregestational diabetes. Outcomes included rates of LGA and preeclampsia. Women were prescribed low-dose aspirin prophylaxis from early pregnancy according to physician discretion after considering preeclampsia risk. Statistical analyses assessed the group overall and with stratification by diabetes type and other preeclampsia risk factors. Of 716 pregnancies, aspirin was prescribed in 296 (41%). Preeclampsia occurred more frequently in women who received aspirin (58 of 296, 20%) than those who did not (39 of 420, 9%, P<0.001). This association was maintained after adjustment for diabetes type and other preeclampsia risk factors (adjusted odds ratio (aOR) 1.78; 95% CI 1.02-3.11). LGA infants were commoner in women with type one diabetes of short duration who took aspirin (aOR 2.21; 95% CI 1.05-4.66). Low-dose aspirin use in women with pregestational diabetes may be associated with an increased risk of preeclampsia. In women with type one diabetes of short duration aspirin use may be associated with an increased risk of LGA infants. The retrospective nature of this study is acknowledged and assessment of such prophylaxis by further studies is warranted.