Preterm delivery and maternal obesity remain common complications in pregnancies with type 1 diabetes-A nationwide study in Sweden.

AIM: A primary goal of obstetric care of women with type 1 diabetes (T1D) is to reduce the risks of preterm birth (PTB). Besides hyperglycaemia, maternal obesity is an important risk factor for PTB in T1D. However, it's unclear if public health efforts decreased risks of maternal obesity and PTB in pregnancies with T1D. We examined time-trends over the last 20 years in the distribution of gestational ages at birth (GA) in offspring of women with T1D in Sweden, and in maternal BMI in the same mothers. METHODS: Population-based cohort study, using data from national registries in Sweden. To capture differences not only in the median values, we used quantile regression models to compare the whole distributions of GA's and early pregnancy BMI between deliveries in 1998-2007 (P1) and 2008-2016 (P2). Multivariable models were adjusted for differences in maternal age, smoking and education between periods 1 and 2. RESULTS: The study included 7639 offspring of women with T1D between 1998 and 2016. The 10% percentile GA, increased with 0.09 days (95% CI: -0.11 to 0.35) between P1 and P2. The 90% percentile for BMI was 1.20 kg/m2 higher (95% CI: 0.57 to 1.83) in P2. Risks of PTB remained stable over time also when adjusting for maternal BMI. CONCLUSION: Despite modern diabetes management, the distribution of GA, and consequently the risk of PTB in T1D, remained unchanged from 1998 to 2016. During the same time, maternal BMI increased, particularly in the already obese.

Maternal body mass index and cerebral palsy in children: A systematic review and dose-response meta-analysis.

BACKGROUND: Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. OBJECTIVES: To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION AND DATA EXTRACTION: Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. SYNTHESIS: Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random-effects model. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. RESULTS: In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta-analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose-response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. CONCLUSION: This meta-analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI.

Mediating processes underlying the associations between maternal obesity and the likelihood of cesarean birth.

BACKGROUND: Pregnant women with obesity are more likely to experience cesarean birth compared to women without obesity. Yet, little is known about the underlying mechanisms. The objective of this study was therefore to evaluate how mediators contribute to the association between obesity and prelabor/intrapartum cesarean birth. METHODS: We retrospectively analyzed Swiss cohort data from 394,812 singleton, cephalic deliveries between 2005 and 2020. Obesity (BMI ≥ 30 kg/m2 ) was defined as the exposure and prelabor or intrapartum cesarean birth as the outcomes. Hypothesized mediators included gestational comorbidities, large-for-gestational-age infant, pregnancy duration >410/7 weeks, slower labor progress, labor induction, and history of cesarean birth. We performed path analyses using generalized structural equation modeling and assessed mediation by a counterfactual approach. RESULTS: Women with obesity had a cesarean birth rate of 39.36% vs. 24.12% in women without obesity. The path models mainly showed positive direct and indirect associations between obesity and cesarean birth. In the total sample, the mediation models explained up to 39.47% (95% CI 36.92-42.02) of the association between obesity and cesarean birth, and up to 57.13% (95% CI 54.10-60.16) when including history of cesarean birth as mediator in multiparous women. Slower labor progress and history of cesarean birth were found to be the most clinically significant mediators. CONCLUSIONS: This study provides empirical insights into how obesity may increase cesarean birth rates through mediating processes. Particularly allowing for a slower labor progress in women with obesity might reduce cesarean birth rates and prevent subsequent repeat cesarean births in multiparous women.

Maternal and long-term offspring outcomes of obesity during pregnancy.

PURPOSE: Obesity`s prevalence is rising in women of reproductive age worldwide and has become the most common medical condition at this age group. Besides, its occurrence is also rising during pregnancy. This condition not only increases the risk of noncommunicable diseases on the mother, such as cardiovascular disease and diabetes, but also transfers this risk to the offspring. METHODS: This is a narrative review based on scientific and review articles on the matter. RESULTS: Obesity is associated with an increased risk of gestational diabetes mellitus, gestational hypertension and preeclampsia, venous thromboembolism, infection, and mental health problems. Furthermore, it has an impact on the progress of labor and induction matters. Regarding offspring outcomes, it is related to higher incidence of congenital anomalies, perinatal mortality, and the occurrence of large for gestational age newborns. Still, it has implications on cardiometabolic risk and neurodevelopment in offspring. CONCLUSION: It is, therefore, imperative to encourage the adoption of healthy lifestyles, especially in the peri-conception and interpregnancy periods. Likewise, there must be support in the multidisciplinary monitoring of these pregnant women to minimize associated complication rates.

Does overweight and obesity have an impact on delivery mode and peripartum outcome in breech presentation? A FRABAT cohort study.

PURPOSE: Obesity is a worldwide and growing issue affecting women in childbearing age, complicating surgical procedures as well as pregnancy. Through a reduction of not necessarily required cesarean deliveries-for instance in pregnancies with breech presentation-obesity mediated and surgery-associated morbidity might be contained. Date on the impact of maternal BMI in vaginally attempted breech delivery is not existing. To give insight into whether an elevated BMI leads to an increased perinatal morbidity in vaginally intended deliveries out of breech presentation, we analyzed delivery outcome of laboring women with a singleton baby in breech presentation with overweight and obesity (BMI ≥ 25 kg/m2) in comparison to women with a BMI of below 25 kg/m2. METHODS: Based on data from January 2004 to December 2020, a cohort study was performed on 1641 women presenting with breech presentation at term (> 37 weeks). The influence of maternal BMI on perinatal outcome was analyzed with Chi2 testing for group differences and logistic regression analysis. Patients with a hyperglycemic metabolism were excluded from the study. RESULTS: Fetal morbidity was not different when patients with a BMI of ≥ 25 kg/m2 (PREMODA morbidity score 2.16%) were compared to patients with a BMI of below 25 kg/m2 (1.97%, p = 0.821). Cesarean delivery rates were significantly higher in overweight and obese women with 43.9% compared to 29.3% (p < 0.0001). BMI and cesarean delivery were significantly associated in a logistic regression analysis (Chi2 coefficient 18.05, p < 0.0001). In successful vaginal deliveries out of breech presentation, maternal perineal injury rates (vaginal birth in normal-BMI women 48.4%; vaginal birth in overweight and obese women: 44.2%; p = 0.273) and rates of manually assisted delivery (vaginal birth in normal-BMI women: 44.4%; vaginal birth in obese and overweight women: 44.2%; p = 0.958) were not different between BMI groups. CONCLUSIONS: Obesity and overweight are not associated with peripartum maternal or newborn morbidity in vaginally attempted breech delivery, if the patient cohort is thoroughly selected and vaginal breech delivery is in an upright maternal position. Reduction of cesarean delivery rates, especially in overweight and obese women might, have an important positive impact on maternal and newborn morbidity.

Association of maternal obesity with preterm birth phenotype and mediation effects of gestational diabetes mellitus and preeclampsia: a prospective cohort study.

BACKGROUND: The association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth. METHODS: We conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-25 kg/m2), overweight (BMI 25-30 kg/m2) and obese (BMI ≥30 kg/m2). Preterm birth was defined as gestational age less than 37 weeks (extremely, < 28 weeks; very, 28-31 weeks; and moderately, 32-36 weeks). The clinical phenotypes of preterm birth included spontaneous preterm birth (spontaneous preterm labor and premature rupture of the membranes) and medically indicated preterm birth. We further analyzed preterm births with GDM or PE. Multivariable logistic regression analysis and causal mediation analysis were performed. RESULTS: Risks of extremely, very, and moderately preterm birth increased with BMI, and the highest risk was observed for obese women with extremely preterm birth (OR 3.43, 95% CI 1.07-10.97). Maternal obesity was significantly associated with spontaneous preterm labor (OR 1.98; 95% CI 1.13-3.47), premature rupture of the membranes (OR 2.04; 95% CI 1.08-3.86) and medically indicated preterm birth (OR 2.05; 95% CI 1.25-3.37). GDM and PE mediated 13.41 and 36.66% of the effect of obesity on preterm birth, respectively. GDM mediated 32.80% of the effect of obesity on spontaneous preterm labor and PE mediated 64.31% of the effect of obesity on medically indicated preterm birth. CONCLUSIONS: Maternal prepregnancy obesity was associated with all phenotypes of preterm birth, and the highest risks were extremely preterm birth and medically indicated preterm birth. GDM and PE partially mediated the association between obesity and preterm birth.

The impact of parity and maternal obesity on the fetal outcomes of a non-selected Lower Saxony population.

OBJECTIVES: Maternal obesity during pregnancy is associated with adverse intrauterine events and fetal outcomes and may increase the risk of obesity and metabolic disease development in offspring. Higher parity, regardless of socioeconomic status, is associated with increased maternal body mass index (BMI). In this study, we examined the relationship between parity, maternal obesity, and fetal outcomes in a large sample of mother-neonate pairs from Lower Saxony, Germany. METHODS: This retrospective cohort study examined pseudonymized data of a non-selected singleton cohort from Lower Saxony's statewide quality assurance initiative. 448,963 cases were included. Newborn outcomes were assessed in relation to maternal BMI and parity. RESULTS: Maternal obesity was associated with an increased risk of placental insufficiency, chorioamnionitis, and fetal distress while giving birth. This effect was present across all parity groups. Fetal presentation did not differ between BMI groups, except for the increased risk of high longitudinal position and shoulder dystocia in obese women. Maternal obesity was also associated with an increased risk of premature birth, low arterial cord blood pH and low 5-min APGAR scores. CONCLUSIONS: Maternal obesity increases the risk of adverse neonatal outcomes. There is a positive correlation between parity and increased maternal BMI. Weight-dependent fetal risk factors increase with parity, while parity-dependent outcomes occur less frequently in multipara. Prevention and intervention programs for women planning to become pregnant can be promising measures to reduce pregnancy and birth complications.

The Risk of Readmission after Early Postpartum Discharge during the COVID-19 Pandemic.

OBJECTIVE: To determine whether early postpartum discharge during the coronavirus disease 2019 (COVID-19) pandemic was associated with a change in the odds of maternal postpartum readmissions. STUDY DESIGN: This is a retrospective analysis of uncomplicated postpartum low-risk women in seven obstetrical units within a large New York health system. We compared the rate of postpartum readmissions within 6 weeks of delivery between two groups: low-risk women who had early postpartum discharge as part of our protocol during the COVID-19 pandemic (April 1-June 15, 2020) and similar low-risk patients with routine postpartum discharge from the same study centers 1 year prior. Statistical analysis included the use of Wilcoxon's rank-sum and chi-squared tests, Nelson-Aalen cumulative hazard curves, and multivariate logistic regression. RESULTS: Of the 8,206 patients included, 4,038 (49.2%) were patients who had early postpartum discharge during the COVID-19 pandemic and 4,168 (50.8%) were patients with routine postpartum discharge prior to the COVID-19 pandemic. The rates of postpartum readmissions after vaginal delivery (1.0 vs. 0.9%; adjusted odds ratio [OR]: 0.75, 95% confidence interval [CI]: 0.39-1.45) and cesarean delivery (1.5 vs. 1.9%; adjusted OR: 0.65, 95% CI: 0.29-1.45) were similar between the two groups. Demographic risk factors for postpartum readmission included Medicaid insurance and obesity. CONCLUSION: Early postpartum discharge during the COVID-19 pandemic was associated with no change in the odds of maternal postpartum readmissions after low-risk vaginal or cesarean deliveries. Early postpartum discharge for low-risk patients to shorten hospital length of stay should be considered in the face of public health crises. KEY POINTS: · Early postpartum discharge was not associated with an increase in odds of hospital readmissions after vaginal delivery.. · Early postpartum discharge was not associated with an increase in odds of hospital readmissions after cesarean delivery.. · Early postpartum discharge for low-risk patients should be considered during a public health crisis..

Reducing intergenerational obesity and diabetes risk.

To address the intergenerational transmission of obesity and diabetes, strategies promoting the health of women of reproductive age appear to be urgently needed. In this narrative review, we summarise what has been learned from many prenatal clinical trials, discuss the emerging evidence from preconception clinical trials and highlight persistent gaps and critical future directions. Most trials tested prenatal interventions that resulted in a limited gestational weight gain of ~1 kg and reduced gestational diabetes by 20-30%. These interventions also reduced macrosomia by 20-40% but had little-to-no impact on other offspring outcomes at birth or beyond. Far fewer trials tested preconception interventions, with almost all designed to improve conception or live-birth rates in overweight or obese women with infertility rather than reduce intergenerational risks in diverse populations. Preconception trials have successfully reduced weight by 3-9 kg and improved markers of glucose homeostasis and insulin resistance by the end of the intervention but whether effects were sustained to conception is unclear. Very few studies have reported offspring outcomes at birth and beyond, with no evidence thus far of beneficial effects on offspring obesity or diabetes risks. Further efforts to develop effective and scalable strategies to reduce risk of obesity and diabetes before conception should be prioritised, especially for diverse and under-resourced populations at disparately high risk of obesity and diabetes. Future clinical trials should include interventions with high potential for dissemination, diverse populations, thorough maternal phenotyping from enrolment through to conception and pregnancy, and rigorous assessment of offspring obesity and diabetes risks from birth onwards, including into the third generation.

Do variations in insulin sensitivity and insulin secretion in pregnancy predict differences in obstetric and neonatal outcomes?

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is generally defined based on glycaemia during an OGTT, but aetiologically includes women with defects in insulin secretion, insulin sensitivity or a combination of both. In this observational study, we aimed to determine if underlying pathophysiological defects evaluated as continuous variables predict the risk of important obstetric and neonatal outcomes better than the previously used dichotomised or categorical approaches. METHODS: Using data from blinded OGTTs at mean gestational week 28 from five Hyperglycemia and Adverse Pregnancy Outcome study centres, we estimated insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral disposition index [DI]) in 6337 untreated women (1090 [17.2%] with GDM as defined by the International Association of Diabetes and Pregnancy Study Groups). Rather than dichotomising these variables (i.e. GDM yes/no) or subtyping by insulin impairment, we related insulin secretion and sensitivity as continuous variables, along with other maternal characteristics, to obstetric and neonatal outcomes using multiple regression and receiver operating characteristic curve analysis. RESULTS: Stratifying by GDM subtype offered superior prediction to GDM yes/no only for neonatal hyperinsulinaemia and pregnancy-related hypertension. Including the DI and the Matsuda score significantly increased the area under the receiver operating characteristic curve (AUROC) and improved prediction for multiple outcomes (large for gestational age [AUROC 0.632], neonatal adiposity [AUROC 0.630], pregnancy-related hypertension [AUROC 0.669] and neonatal hyperinsulinaemia [AUROC 0.688]). Neonatal hypoglycaemia was poorly predicted by all models. Combining the DI and the Matsuda score with maternal characteristics substantially improved the predictive power of the model for large for gestational age, neonatal adiposity and pregnancy-related hypertension. CONCLUSION/INTERPRETATION: Continuous measurement of insulin secretion and insulin sensitivity combined with basic clinical variables appeared to be superior to GDM (yes/no) or subtyping by insulin secretion and/or sensitivity impairment in predicting obstetric and neonatal outcomes in a multi-ethnic cohort. Graphical abstract.

Maternal obesity increases the risk and severity of NAFLD in offspring.

BACKGROUND & AIMS: Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear. METHODS: Through the nationwide ESPRESSO cohort study we identified all individuals ≤25 years of age in Sweden with biopsy-verified NAFLD diagnosed between 1992 and 2016 (n = 165). These were matched by age, sex, and calendar year with up to 5 controls (n = 717). Through linkage with the nationwide Swedish Medical Birth Register (MBR) we retrieved data on maternal early-pregnancy BMI, and possible confounders, in order to calculate adjusted odds ratios (aORs) for NAFLD in offspring. RESULTS: Maternal BMI was associated with NAFLD in offspring: underweight (aOR 0.84; 95% CI 0.14-5.15), normal weight (reference, aOR 1), overweight (aOR 1.51; 0.95-2.40), and obese (aOR 3.26; 1.72-6.19) women. Severe NAFLD (biopsy-proven fibrosis or cirrhosis) was also more common in offspring of overweight (aOR 1.94; 95% CI 0.96-3.90) and obese (aOR 3.67; 95% CI 1.61-8.38) mothers. Associations were similar after adjusting for maternal pre-eclampsia and gestational diabetes. Socio-economic parameters (smoking, mother born outside the Nordic countries and less than 10 years of basic education) were also associated with NAFLD in offspring but did not materially alter the effect size of maternal BMI in a multivariable model. CONCLUSIONS: This nationwide study found a strong association between maternal overweight/obesity and future NAFLD in offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect this finding, suggesting that maternal obesity is an independent risk factor for NAFLD in offspring. LAY SUMMARY: In a study of all young persons in Sweden with a liver biopsy consistent with fatty liver, the authors found that compared to matched controls, the risk of fatty liver was much higher in those with obese mothers. This was independent of available confounders and suggests that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.

Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation.

OBJECTIVE: Recent evidence indicates that levels of breast milk (BM) hormones such as leptin can fluctuate with maternal adiposity, suggesting that BM hormones may signal maternal metabolic and nutritional environments to offspring during postnatal development. The hormone apelin is highly abundant in BM but its regulation during lactation is completely unknown. Here, we evaluated whether maternal obesity and overnutrition impacted BM apelin and leptin levels in clinical cohorts and lactating rats. METHODS: BM and plasma samples were collected from normal-weight and obese breastfeeding women, and from lactating rats fed a control or a high fat (HF) diet during lactation. Apelin and leptin levels were assayed by ELISA. Mammary gland (MG) apelin expression and its cellular localization in lactating rats was measured by quantitative RT-PCR and immunofluorescence, respectively. RESULTS: BM apelin levels increased with maternal BMI, whereas plasma apelin levels decreased. BM apelin was also positively correlated with maternal insulin and C-peptide levels. In rats, maternal HF feeding exclusively during lactation was sufficient to increase BM apelin levels and decrease its plasma concentration without changing body weight. In contrast, BM leptin levels increased with maternal BMI in humans, but did not change with maternal HF feeding during lactation in rats. Apelin is highly expressed in the rat MG during lactation and was mainly localized to mammary myoepithelial cells. We found that MG apelin gene expression was up-regulated by maternal HF diet and positively correlated with BM apelin content and maternal insulinemia. CONCLUSIONS: Our study indicates that BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.

Child physical activity as a modifier of the relationship between prenatal exposure to maternal overweight/obesity and neurocognitive outcomes in offspring.

BACKGROUND/OBJECTIVES: With rising obesity rates among pregnant women, more children are exposed in utero to maternal obesity. In prior epidemiological studies, exposure to maternal obesity was associated with lower intelligence quotient (IQ) scores and worse cognitive abilities in offspring. Further studies have shown that offspring exposed to maternal obesity, exhibit differences in the white matter microstructure properties, fractional anisotropy (FA) and mean diffusivity (MD). In contrast, physical activity was shown to improve cognition and white matter microstructure during childhood. We examined if child physical activity levels modify the relationship between prenatal exposure to maternal obesity with IQ and white matter microstructure in offspring. SUBJECTS/METHODS: One hundred children (59% girls) age 7-11 years underwent brain magnetic resonance imaging and IQ testing. Maternal pre-pregnancy BMI was abstracted from electronic medical records. White matter was assessed using diffusion tensor imaging with the measures, global FA, MD. The 3-day physical activity recall was used to measure moderate-to-vigorous physical activity and vigorous physical activity (VPA). Linear regression was used to test for interactions between prenatal exposure to maternal overweight/obesity and child PA levels on child IQ and global FA/MD. RESULTS: The relationship between prenatal exposure to maternal overweight/obesity and child IQ and global FA varied by child VPA levels. Children exposed to mothers with overweight/obesity who engaged in more VPA had higher IQ scores and global FA compared to exposed children who engaged in less VPA. Associations were independent of child age, sex, BMI Z-score and socioeconomic status. Children born to normal-weight mothers did not differ in either IQ or global FA by time in VPA. CONCLUSIONS: Our findings support findings in rodent models and suggest that VPA during childhood modifies the relationship between prenatal exposure to maternal obesity and child IQ and white matter microstructure.

Role of maternal glucose metabolism in the association between maternal BMI and neonatal size and adiposity.

BACKGROUND/OBJECTIVE: One potential mechanism by which maternal obesity impacts fetal growth is through hyperglycemia below the threshold for gestational diabetes. Data regarding which measures of maternal glucose metabolism mediate this association is sparse. The objectives of this study were to (i) quantify the associations of maternal pre-pregnancy body mass index (BMI) with neonatal size and adiposity and (ii) examine the role of markers of maternal glucose metabolism as mediators in these associations. SUBJECTS/METHODS: This is a secondary analysis of 6,379 mother-infant dyads from the Hyperglycemia and Adverse Pregnancy Outcome cohort. Markers of glucose metabolism, including plasma glucose and c-peptide values, Stumvoll first-phase estimate, modified Matsuda index, and oral disposition index were measured and calculated from an oral glucose tolerance test (OGTT) between 24- and 32-weeks' gestation. We calculated the direct effect of maternal BMI category, measured at the time of the OGTT and regressed to estimate pre-pregnancy BMI, on neonatal (1) birth weight (BW), (2) fat mass (FM), (3) % body fat (BF%), and (4) sum of skinfold thickness (sSFT). We then calculated the indirect effect of BMI category on these measures through markers of glucose metabolism. RESULTS: Maternal BMI category was positively associated with neonatal BW, FM, BF%, and sSFT. Additionally, mothers who were overweight or obese had higher odds of delivering an infant with BW, FM, BF%, or sSFT >90th percentile. Fasting glucose and c-peptide values were the strongest mediators in the linear associations between maternal BMI category and neonatal size and adiposity. CONCLUSIONS: Maternal overweight and obesity were associated with higher odds of neonatal BW and adiposity >90th percentile. Fasting measures of glucose metabolism were the strongest mediators of these associations, suggesting that future studies should investigate whether incorporation of these markers in pregnant women with obesity may improve prediction of neonatal size and adiposity.

Performance of early risk assessment tools to predict the later development of gestational diabetes.

BACKGROUND: Several prognostic models for gestational diabetes mellitus (GDM) are provided in the literature; however, their clinical significance has not been thoroughly evaluated, especially with regard to application at early gestation and in accordance with the most recent diagnostic criteria. This external validation study aimed to assess the predictive accuracy of published risk estimation models for the later development of GDM at early pregnancy. METHODS: In this cohort study, we prospectively included 1132 pregnant women. Risk evaluation was performed before 16 + 0 weeks of gestation including a routine laboratory examination. Study participants were followed-up until delivery to assess GDM status according to the IADPSG 2010 diagnostic criteria. Fifteen clinical prediction models were calculated according to the published literature. RESULTS: Gestational diabetes mellitus was diagnosed in 239 women, that is 21.1% of the study participants. Discrimination was assessed by the area under the ROC curve and ranged between 60.7% and 76.9%, corresponding to an acceptable accuracy. With some exceptions, calibration performance was poor as most models were developed based on older diagnostic criteria with lower prevalence and therefore tended to underestimate the risk of GDM. The highest variable importance scores were observed for history of GDM and routine laboratory parameters. CONCLUSIONS: Most prediction models showed acceptable accuracy in terms of discrimination but lacked in calibration, which was strongly dependent on study settings. Simple biochemical variables such as fasting glucose, HbA1c and triglycerides can improve risk prediction. One model consisting of clinical and laboratory parameters showed satisfactory accuracy and could be used for further investigations.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

The impact of physical activity during pregnancy on labor and delivery.

BACKGROUND: Physical activity in pregnancy is associated with decreased risks of adverse pregnancy outcomes such as gestational diabetes and preeclampsia. However, the relationship between the amount and type of physical activity during pregnancy and subsequent labor outcomes remains unclear. OBJECTIVE: This study aimed to test the hypothesis that higher levels of physical activity across different lifestyle domains in pregnancy are associated with a shorter duration of labor. STUDY DESIGN: This study is a secondary analysis of a prospective cohort study in which patients with singleton pregnancies without a major fetal anomaly were administered the Kaiser Physical Activity Survey in each trimester. The Kaiser Physical Activity Survey was designed specifically to quantify various types of physical activities in women and includes 4 summative indices-housework/caregiving, active living habits, sports, and occupation. The study included women at full-term gestations admitted for induction of labor or spontaneous labor. The primary outcome of this analysis was duration of the second stage of labor. Secondary outcomes were duration of the active stage, prolonged first and second stage, mode of delivery, rates of second-stage cesarean delivery, operative vaginal delivery, severe perineal lacerations, and postpartum hemorrhage. These outcomes were compared between patients with and without high physical activity levels, defined as overall Kaiser Physical Activity Survey score ≥75th percentile in the third trimester. Multivariable logistic regression was used to adjust for obesity and epidural use. In addition, a subgroup analysis of nulliparous patients was performed. RESULTS: A total of 811 patients with complete Kaiser Physical Activity Survey data in the third trimester were included in this analysis. The median Kaiser Physical Activity Survey score was 9.5 (8.2-10.8). Of the 811 patients, 203 (25%) had higher levels of physical activity in pregnancy. There was no difference in the duration of the second stage of labor between patients with and without higher physical activity levels (1.29±2.94 vs 0.97±2.08 hours; P=.15). The duration of active labor was significantly shorter in patients with higher levels of physical activity (5.77±4.97 vs 7.43±6.29 hours; P=.01). Patients with higher physical activity levels were significantly less likely to have a prolonged first stage (9.8% vs 19.4%; P<.01; adjusted relative risk, 0.55; 95% confidence interval, 0.34-0.83). However, rates of prolonged second-stage cesarean delivery, operative vaginal deliveries, and perineal lacerations were similar between the 2 groups. CONCLUSION: Patients who are more physically active during pregnancy have a shorter duration of active labor.

The risk of recurrent small-for-gestational-age infants at term is dependent on the number of previously affected births.

BACKGROUND: Small-for-gestational-age infants are at a substantially increased risk of perinatal complications, but the risk of recurrent small-for-gestational-age is not well known, particularly because there are many demographic and obstetrical factors that interact and modify this risk. We investigated the relationship between previous small-for-gestational-age births and the risk of recurrence at term in a large Australian cohort. OBJECTIVE: We aimed to identify key demographic and obstetrical variables that influence the risk of recurrence of a small-for-gestational-age infant at term. The primary outcome measure was the odds of recurrence of small-for-gestational-age in subsequent pregnancies up to a maximum of 4 consecutive term births. STUDY DESIGN: This was a retrospective analysis of women who had more than 1 consecutive nonanomalous, singleton, term live births between July 1997 and September 2018 at the Mater Mother's Hospital in Brisbane, Australia. Women with multiple pregnancy, preterm birth, or major congenital malformations were excluded. Small-for-gestational-age was defined as birthweight at the <10th centile. We calculated the odds of recurrence depending on the number of previous small-for-gestational-age infants and if only the preceding infant was small-for-gestational-age. The study population was dichotomized into small-for-gestational-age and non-small-for-gestational-age for each consecutive pregnancy. Univariate analyses compared baseline demographic and obstetrical characteristics followed by logistic regression modeling to determine the odds of recurrence in the second, third, and fourth pregnancies. RESULTS: The final study comprised 24,819 women. The proportion of women who had a small-for-gestational-age infant in their first pregnancy was 9.4%, whereas the proportion of women who had a small-for-gestational-age infant in their second, third, and fourth pregnancies after the birth of a previous small-for-gestational-age infant were 20.5% (479 of 2338), 24.6% (63 of 256), and 30.4% (14 of 46), respectively. Regardless of parity, the odds of recurrence increased if the preceding infant was small-for-gestational-age. The odds of recurrence increased markedly if there was more than 1 previous small-for-gestational-age infant. In women with 3 previous small-for-gestational-age infants, the adjusted odds of another small-for-gestational-age infant were 66.00 (95% confidence interval, 11.35-383.76). Maternal age, body mass index, ethnicity, and smoking were significant risk factors for recurrent small-for-gestational-age. However, maternal diabetes mellitus or hypertension, either in a previous or current pregnancy, did not influence the risk of recurrence. CONCLUSION: The risk of recurrence in a subsequent pregnancy increased if there was a previous small-for-gestational-age birth. Women with consecutive small-for-gestational-age infants were at the highest risk of recurrence. Our results highlight that women with a previous small-for-gestational-age infant are at a substantial risk of another small infant and need to be counseled and monitored appropriately.

Maternal weight gain and pregnancy outcomes in twin gestations.

BACKGROUND: Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population. OBJECTIVE: This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group. RESULTS: A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the <10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the <10th centile. Associations were less consistent in the overweight and obese groups. CONCLUSION: These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies.

Predicting obstetrical anal sphincter injuries in patients who undergo vaginal birth after cesarean delivery.

BACKGROUND: Women with a history of previous cesarean delivery must weigh the numerous potential risks and benefits of elective repeat cesarean delivery or trial of labor after cesarean delivery. Notably, 1 important risk of vaginal delivery is obstetrical anal sphincter injuries. Furthermore, the rate of obstetrical anal sphincter injuries is high among women undergoing vaginal birth after cesarean delivery. However, the risk of obstetrical anal sphincter injuries is not routinely included in the trial of labor after cesarean delivery counseling, and there is no tool available to risk stratify obstetrical anal sphincter injuries among women undergoing vaginal birth after cesarean delivery. OBJECTIVE: This study aimed to develop and validate a predictive model to estimate the risk of obstetrical anal sphincter injuries in the setting of vaginal birth after cesarean delivery population to improve antenatal counseling of patients regarding risks of trial of labor after cesarean delivery. STUDY DESIGN: This study was a secondary subgroup analysis of the Maternal-Fetal Medicine Units Network Trial of Labor After Cesarean Delivery prospective cohort (1999-2002). We identified women within the Maternal-Fetal Medicine Units Network cohort with 1 previous cesarean delivery followed by a term vaginal birth after cesarean delivery. This Maternal-Fetal Medicine Units Network Vaginal Birth After Cesarean Delivery cohort was stratified into 2 groups based on the presence of obstetrical anal sphincter injuries, and baseline characteristics were compared with bivariate analysis. Significant covariates in bivariate testing were included in a backward stepwise logistic regression model to identify independent risk factors for obstetrical anal sphincter injuries and generate a predictive model for obstetrical anal sphincter injuries in the setting of vaginal birth after cesarean delivery. Internal validation was performed using bootstrapped bias-corrected estimates of model concordance indices, Brier scores, Hosmer-Lemeshow chi-squared values, and calibration plots. External validation was performed using data from a single-site retrospective cohort of women with a singleton vaginal birth after cesarean delivery from January 2011 to December 2016. RESULTS: In this study, 10,697 women in the Maternal-Fetal Medicine Units Network Trial of Labor After Cesarean Delivery cohort met the inclusion criteria, and 669 women (6.3%) experienced obstetrical anal sphincter injuries. In the model, factors independently associated with obstetrical anal sphincter injuries included use of forceps (adjusted odds ratio, 5.08; 95% confidence interval, 4.10-6.31) and vacuum assistance (adjusted odds ratio, 2.64; 95% confidence interval, 2.02-3.44), along with increasing maternal age (adjusted odds ratio, 1.05; 95% confidence interval, 1.04-1.07 per year), body mass index (adjusted odds ratio, 0.99; 95% confidence interval, 0.97-1.00 per unit kg/m2), previous vaginal delivery (adjusted odds ratio, 0.19; 95% confidence interval, 0.15-0.23), and tobacco use during pregnancy (adjusted odds ratio, 0.59; 95% confidence interval, 0.43-0.82). Internal validation demonstrated appropriate discrimination (concordance index, 0.790; 95% confidence interval, 0.771-0.808) and calibration (Brier score, 0.047). External validation used data from 1266 women who delivered at a tertiary healthcare system, with appropriate model discrimination (concordance index, 0.791; 95% confidence interval, 0.735-0.846) and calibration (Brier score, 0.046). The model can be accessed at oasisriskscore.xyz. CONCLUSION: Our model provided a robust, validated estimate of the probability of obstetrical anal sphincter injuries during vaginal birth after cesarean delivery using known antenatal risk factors and 1 modifiable intrapartum risk factor and can be used to counsel patients regarding risks of trial of labor after cesarean delivery compared with risks of elective repeat cesarean delivery.