Development and evaluation of machine learning models for predicting large-for-gestational-age newborns in women exposed to radiation prior to pregnancy.

INTRODUCTION: The correlation between radiation exposure before pregnancy and abnormal birth weight has been previously proven. However, for large-for-gestational-age (LGA) babies in women exposed to radiation before becoming pregnant, there is no prediction model yet. MATERIAL AND METHODS: The data were collected from the National Free Preconception Health Examination Project in China. A sum of 455 neonates (42 SGA births and 423 non-LGA births) were included. A training set (n = 319) and a test set (n = 136) were created from the dataset at random. To develop prediction models for LGA neonates, conventional logistic regression (LR) method and six machine learning methods were used in this study. Recursive feature elimination approach was performed by choosing 10 features which made a big contribution to the prediction models. And the Shapley Additive Explanation model was applied to interpret the most important characteristics that affected forecast outputs. RESULTS: The random forest (RF) model had the highest average area under the receiver-operating-characteristic curve (AUC) for predicting LGA in the test set (0.843, 95% confidence interval [CI]: 0.714-0.974). Except for the logistic regression model (AUC: 0.603, 95%CI: 0.440-0.767), other models' AUCs displayed well. Thereinto, the RF algorithm's final prediction model using 10 characteristics achieved an average AUC of 0.821 (95% CI: 0.693-0.949). CONCLUSION: The prediction model based on machine learning might be a promising tool for the prenatal prediction of LGA births in women with radiation exposure before pregnancy.

Diagnosis and Management of Macrosomia and Shoulder Dystocia: A Comprehensive Review of Major Guidelines.

Importance: Macrosomia represents the most significant risk factor of shoulder dystocia (SD), which is a severe and emergent complication of vaginal delivery. They are both associated with adverse pregnancy outcomes. Objective: The aim of this study was to review and compare the most recently published influential guidelines on the diagnosis and management of fetal macrosomia and SD. Evidence Acquisition: A comparative review of guidelines from the American College of Obstetricians and Gynecologists (ACOG), the Royal College of Obstetricians and Gynaecologists, the National Institute for Health and Care Excellence, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), and the Department for Health and Wellbeing of the Government of South Australia on macrosomia and SD was conducted. Results: The ACOG and RANZCOG agree that macrosomia should be defined as birthweight above 4000-4500 g regardless of the gestational age, whereas the National Institute for Health and Care Excellence defines macrosomia as an estimated fetal weight above the 95th percentile. According to ACOG and RANZCOG, ultrasound scans and clinical estimates can be used to rule out fetal macrosomia, although lacking accuracy. Routine induction of labor before 39 weeks of gestation with the sole indication of suspected fetal macrosomia is unanimously not recommended, but an individualized counseling should be provided. Exercise, appropriate diet, and prepregnancy bariatric surgery are mentioned as preventive measures. There is also consensus among the reviewed guidelines regarding the definition and the diagnosis of SD, with the "turtle sign" being the most common sign for its recognition as well as the poor predictability of the reported risk factors. Moreover, there is an overall agreement on the algorithm of SD management with McRoberts technique suggested as first-line maneuver. In addition, appropriate staff training, thorough documentation, and time keeping are crucial aspects of SD management according to all medical societies. Elective delivery for the prevention of SD is discouraged by all the reviewed guidelines. Conclusions: Macrosomia is associated not only with SD but also with maternal and neonatal complications. Similarly, SD can lead to permanent neurologic sequalae, as well as perinatal death if managed in a suboptimal way. Therefore, it is crucial to develop consistent international practice protocols for their prompt diagnosis and effective management in order to safely guide clinical practice and improve pregnancy outcomes.

One-step vs 2-step gestational diabetes mellitus screening and pregnancy outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: This was a systematic review and meta-analysis comparing maternal and neonatal outcomes of patients screened with the 1-step or 2-step screening method for gestational diabetes mellitus. DATA SOURCES: PubMed, Scopus, Cochrane, ClinicalTrials.gov, and LILACS were searched from inception up to September 2022. STUDY ELIGIBILITY CRITERIA: Only randomized controlled trials were included. Studies that had overlapping populations were excluded (International Prospective Register of Systematic Review registration number: CRD42022358903). METHODS: Risk ratios were computed with 95% confidence intervals by 2 authors. Unpublished data were requested. Large for gestational age was the primary outcome. RESULTS: The search yielded 394 citations. Moreover, 7 randomized controlled trials met the inclusion criteria. A total of 54,650 participants were screened for gestational diabetes mellitus by either the 1-step screening method (n=27,163) or the 2-step screening method (n=27,487). For large for gestational age, there was no significant difference found between the groups (risk ratio, 0.99; 95% confidence interval, 0.93-1.05; I2=0%). Newborns of patients who underwent 1-step screening had higher rates of neonatal hypoglycemia (risk ratio, 1.24; 95% confidence interval, 1.14-1.34; I2=0%) and neonatal intensive care unit admissions (risk ratio, 1.13; 95% confidence interval, 1.04-1.21; I2=0%) than newborns of patients who underwent 2-step screening. Patients in the 1-step screening method group were more likely to be diagnosed with gestational diabetes mellitus (risk ratio, 1.73; 95% confidence interval, 1.44-2.09; I2=80%) than patients in the 2-step screening method group. In addition, among trials that tested all patients before randomization and excluded patients with pregestational diabetes mellitus, newborns were more likely to have macrosomia (risk ratio, 1.27; 95% confidence interval, 1.21-1.34; I2=0%). Overall risk of bias assessment was of low concern. CONCLUSION: Large for gestational age did not differ between patients screened using the 1-step screening method and those screened using the 2-step screening method. However, patients randomized to the 1-step screening method had higher rates of neonatal hypoglycemia and neonatal intensive care unit admission and maternal gestational diabetes mellitus diagnosis than the patients randomized to the 2-step screening method.

Periportal hepatocyte proliferation at midgestation governs maternal glucose homeostasis in mice.

The maternal liver is challenged by metabolic demands throughout pregnancy. However, hepatocyte dynamics and their physiological significance in pregnancy remain unclear. Here, we show in mice that hepatocyte proliferation is spatiotemporally regulated in each liver lobular zone during pregnancy, with transient proliferation of periportal and pericentral hepatocytes during mid and late gestation, respectively. Using adeno-associated virus (AAV)-8-mediated expression of the cell cycle inhibitor p21 in hepatocytes, we show that inhibition of hepatocyte proliferation during mid, but not late, gestation impairs liver growth. Transcriptionally, genes involved in glucose/glycogen metabolism are downregulated in late pregnancy when midgestational hepatocyte proliferation is attenuated. In addition, hepatic glycogen storage is abolished, with concomitant elevated blood glucose concentrations, glucose intolerance, placental glycogen deposition, and fetal overgrowth. Laser capture microdissection and RNA-seq analysis of each liver lobular zone show zone-specific changes in the transcriptome during pregnancy and identify genes that are periportally expressed at midgestation, including the hyaluronan-mediated motility receptor (Hmmr). Knockdown of Hmmr in hepatocytes by AAV8-shHmmr suppresses periportal hepatocyte proliferation at midgestation and induces impaired hepatic glycogen storage, glucose intolerance, placental glycogen deposition and fetal overgrowth. Our results suggest that periportal hepatocyte proliferation during midgestation is critical for maternal glycogen metabolism and fetal size.

Impact of placental mTOR deficiency on peripheral insulin signaling in adult mice offspring.

Suboptimal in utero environments such as poor maternal nutrition and gestational diabetes can impact fetal birth weight and the metabolic health trajectory of the adult offspring. Fetal growth is associated with alterations in placental mechanistic target of rapamycin (mTOR) signaling; it is reduced in fetal growth restriction and increased in fetal overgrowth. We previously reported that when metabolically challenged by a high-fat diet, placental mTORKO (mTORKOpl) adult female offspring develop obesity and insulin resistance, whereas placental TSC2KO (TSC2KOpl) female offspring are protected from diet-induced obesity and maintain proper glucose homeostasis. In the present study, we sought to investigate whether reducing or increasing placental mTOR signaling in utero alters the programming of adult offspring metabolic tissues preceding a metabolic challenge. Adult male and female mTORKOpl, TSC2KOpl, and respective controls on a normal chow diet were subjected to an acute intraperitoneal insulin injection. Upon insulin stimulation, insulin signaling via phosphorylation of Akt and nutrient sensing via phosphorylation of mTOR target ribosomal S6 were evaluated in the offspring liver, white adipose tissue, and skeletal muscle. Among tested tissues, we observed significant changes only in the liver signaling. In the male mTORKOpl adult offspring liver, insulin-stimulated phospho-Akt was enhanced compared to littermate controls. Basal phospho-S6 level was increased in the mTORKOpl female offspring liver compared to littermate controls and did not increase further in response to insulin. RNA sequencing of offspring liver identified placental mTORC1 programming-mediated differentially expressed genes. The expression of major urinary protein 1 (Mup1) was differentially altered in female mTORKOpl and TSC2KOpl offspring livers and we show that MUP1 level is dependent on overnutrition and fasting status. In summary, deletion of placental mTOR nutrient sensing in utero programs hepatic response to insulin action in a sexually dimorphic manner. Additionally, we highlight a possible role for hepatic and circulating MUP1 in glucose homeostasis that warrants further investigation.

The duration of estrogen treatment before progesterone application does not affect neonatal and perinatal outcomes in frozen embryo transfer cycles.

Objective: To explore whether the duration of estrogen treatment before progesterone application affects neonatal and perinatal outcomes in artificial frozen embryo transfer (FET) cycles. Methods: This was a retrospective cohort study. Patients who underwent FET via artificial cycles and delivered a singleton live birth between January 2015 and August 2019 were included in the analysis. According to the duration of estrogen treatment before progesterone application, we divided the cycles into four groups: ①≤12 days, ②13-15 days, ③16-19 days, and ④≥20 days. The '≤12 days group' was considered the reference group. The main outcome measures were preterm birth (PTB), small-for-gestational age (SGA), low birth weight (LBW), macrosomia, large-for-gestational age (LGA), gestational diabetes mellitus (GDM), gestational hypertension, premature rupture and placenta previa. Results: Overall, 2010 FET cycles with singleton live births were included for analysis. Cycles were allocated to four groups according to the duration of estrogen treatment before progesterone application: ①≤12 days (n=372), ②13-15 days (n=745), ③16-19 days (n=654), ④≥20 days (n=239). The neonatal outcomes, including PTB, SGA, LBW, macrosomia and LGA, were comparable among the groups (P=0.328, P=0.390, P=0.551, P=0.565, P=0.358). The rates of gestational hypertension, premature rupture and placenta previa (P=0.676, P=0.662, P=0.211) were similar among the groups. The rates of GDM among the four groups were 4.0% (15/372), 6.7% (50/745), 6.4% (42/654), and 11.3% (27/239), with statistical significance (P=0.006). After multiple logistic regression analysis, the duration of estrogen treatment did not affect the rate of GDM or other outcomes. Conclusion: The estrogen treatment duration before progesterone application does not affect neonatal and perinatal outcomes in single frozen blastocyst transfer cycles.

Comparison of the neonatal outcomes of progestin-primed ovarian stimulation and flexible GnRH antagonist protocols: a propensity score-matched cohort study.

Objective: To compare the neonatal outcomes of progestin-primed ovarian stimulation (PPOS) and flexible gonadotropin-releasing hormone (GnRH) antagonist protocols. Methods: This was a retrospective propensity score-matched (PSM) cohort study. Women who underwent their first frozen embryo transfer (FET) cycle with freezing of all embryos followed by PPOS or GnRH antagonist protocols between January 2016 and January 2022 were included. Patients using PPOS were matched with the patients using GnRH antagonist at a 1:1 ratio. The main focus of this study was the neonatal outcomes of singleton live births, including preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), macrosomia and large for gestational age (LGA). Results: After 1:1 PSM, a total of 457 PPOS and 457 GnRH antagonist protocols were included for analysis. The average starting dose of gonadotropin (275.1 ± 68.1 vs. 249.3 ± 71.3, P<0.01) and total dose of gonadotropin (2799.6 ± 579.9 vs. 2634.4 ± 729.1, P<0.01) were significantly higher in the PPOS protocol than in the GnRH antagonist protocol. The other baseline and cycle characteristics were comparable between the two protocols. The rates of PTB (P=0.14), LBW (P=0.11), SGA (P=0.31), macrosomia (P=0.11) and LGA (P=0.49) did not differ significantly between the two groups. A total of 4 patients in the PPOS group and 3 patients in the GnRH antagonist group qualified as having congenital malformations. Conclusion: PPOS resulted in singleton neonatal outcomes similar to those of a GnRH antagonist protocol. The application of the PPOS protocol is a safe option for infertility patients.

Fatal leukodystrophy in Costello syndrome: a case report.

BACKGROUND: Costello syndrome (CS) is a rare genetic condition characterized by dysregulation of the signaling pathway, phenotypic alteration due to fetal macrosomia or growth retardation, facial abnormalities, loose skin, cardiovascular abnormalities, and a variable degree of intellectual disability. CASE PRESENTATION: We describe the case of a 20-month-old male patient with fetal macrosomia and polyhydramnios, presenting psychomotor development delay and growth limitation during the first months of life. CS was diagnosed at four months of age after detecting a variant of the HRAS gene c.35G > C (p.G12A). A clinical description of his condition was recorded throughout his life, including cardiovascular diseases, endocrine disorders, and recurrent infections. At 20 months of age, after presenting events of marked hypotonia and generalized seizures, brain magnetic resonance revealed symmetrical lesions of the infra- and supratentorial white matter in both cerebral hemispheres, which resulted in the diagnosis of cerebral leukodystrophy. The patient had a rapid and progressive deterioration that eventually led to death. CONCLUSIONS: This is the first report of a case of CS in Peru. In addition, this is a case that presented with multisystemic conditions culminating in leukodystrophy, which is a rare event according to the literature.

Association of Fine Particulate Matter and Its Components with Macrosomia: A Nationwide Birth Cohort Study of 336 Chinese Cities.

To examine the associations between macrosomia risk and exposure to fine particulate matter (PM2.5) and its chemical components during pregnancy, we collected birth records between 2010 and 2015 in mainland China from the National Free Preconception Health Examination Project and used satellite-based models to estimate concentrations of PM2.5 mass and five main components, namely, black carbon (BC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), and ammonium (NH4+). Associations between macrosomia risk and prenatal exposure to PM2.5 were examined by logistic regression analysis, and the sensitive subgroups were explored by stratified analyses. Of the 3,248,263 singleton newborns from 336 cities, 165,119 (5.1%) had macrosomia. Each interquartile range increase in concentration of PM2.5 during the entire pregnancy was associated with increased risk of macrosomia (odds ratio (OR) = 1.18; 95% confidence interval (CI), 1.17-1.20). Among specific components, the largest effect estimates were found on NO3- (OR = 1.36; 95% CI, 1.35-1.38) followed by OC (OR = 1.23; 95% CI, 1.22-1.24), NH4+ (OR = 1.22; 95% CI, 1.21-1.23), and BC (OR = 1.21; 95% CI, 1.20-1.22). We also that found boys, women with a normal or lower prepregnancy body mass index, and women with irregular or no folic acid supplementation experienced higher risk of macrosomia associated with PM2.5 exposure.

First trimester sCD40L levels associated with adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Backgrounds: It remained unclear whether isolated positive thyroid peroxidative antibodies (TPOAb) were associated with adverse maternal and neonatal outcomes. The purpose of this study was to observe adverse neonatal outcomes among euthyroid pregnant women with positive TPOAb and to investigate the underlying risk factors. Methods: Euthyroid pregnant women with TPOAb positivity were enrolled and followed up in our study. Adverse neonatal outcomes such as preterm birth, low birth weight, and fetal macrosomia were observed. Clinical data in the first trimester were collected and compared between groups with or without adverse neonatal outcomes. Maternal serum soluble CD40 ligand (sCD40L) was also measured at the same time. Results: A total of 176 euthyroid pregnant women with TPOAb positivity were finally enrolled and analyzed in our study. Thirty-nine (22.16%) euthyroid women with TPOAb positivity were found to have adverse neonatal outcomes. Thirteen participants received assisted reproductive technology (ART) in our study, and seven participants were in the adverse neonatal outcome group. Preterm birth, low birth weight, and fetal macrosomia were the most common comorbidities. The proportion of receiving ART and the levels of sCD40L and platelet were significantly higher in the adverse neonatal outcome group (all P < 0.05). Multivariate regression analysis showed that sCD40L and receiving ART were the independent risk factors for adverse neonatal outcomes. The odds ratio values of sCD40L higher than 5.625 ng/ml were 2.386 [95% confidence interval (CI) = 1.017 to 5.595; P = 0.046] for overall adverse neonatal outcome, 3.900 (95% CI = 1.194 to 12.738; P = 0.024) for preterm birth, and 3.149 (95% CI = 0.982 to 10.101; P = 0.054) for low birth weight. Conclusions: Approximately one of the four euthyroid women with TPOAb positivity might have adverse neonatal outcomes. Measurement of sCD40L in first trimester might have a predictive value for adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Evaluation of pregnancy and neonatal outcomes according to the phenotypic types of polycystic ovary syndrome: A prospective study.

OBJECTIVE: We aimed to compare pregnancy and neonatal outcomes in the phenotypic subtypes of patients with polycystic ovary syndrome (PCOS). METHODS: This prospective cohort included the patients with PCOS (n = 121) diagnosed according to the presence of androgen excess, ovulatory dysfunction, and/or polycystic ovary morphology and healthy controls (n = 125). We stratified PCOS as phenotype A (n = 45), phenotype B (n = 8), phenotype C (n = 32) and phenotype D (n = 35) and followed throughout pregnancy, comparing their outcomes. RESULTS: The study population had a mean age of 28.7 ± 4.9 years and a mean BMI of 31.6 kg/m2 with no difference between the groups. Primary cesarean deliveries were significantly more common in PCOS patients (23.3%) than in the control group (17.6%, P = 0.021). The phenotype A group had significantly higher rates of gestational diabetes mellitus (GDM) (42.2%, P < 0.001) and fetal macrosomia (14.6%, P = 0.002) compared with the control group (4.8% and 0.8%m respectively). We detected a significantly lower rate of normal risk score on the double screening test in the PCOS group (59.0%) than in the control group (75.4%) and in the other groups (P = 0.001). CONCLUSION: The rates of GDM, fetal macrosomia, and cesarean section were higher in the PCOS group, depending on the phenotype. We observed changes in risk calculation according to phenotypic types at aneuploidy screening.

Association between excessive fetal growth and maternal cancer in Shanghai, China: a large, population-based cohort study.

The prevalence of high birth weight or large for gestational age (LGA) infants is increasing, with increasing evidence of pregnancy-related factors that may have long-term impacts on the health of the mother and baby. We aimed to determine the association between excessive fetal growth, specifically LGA and macrosomia, and subsequent maternal cancer by performing a prospective population-based cohort study. The data set was based on the Shanghai Birth Registry and Shanghai Cancer Registry, with medical records from the Shanghai Health Information Network as a supplement. Macrosomia and LGA prevalence was higher in women who developed cancer than in women who did not. Having an LGA child in the first delivery was associated with a subsequently increased risk of maternal cancer (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.11). Additionally, in the last and heaviest deliveries, there were similar associations between LGA births and maternal cancer rates (HR = 1.08, 95% CI 1.04-1.12; HR = 1.08, 95% CI 1.05-1.12, respectively). Furthermore, a substantially increased trend in the risk of maternal cancer was associated with birth weights exceeding 2500 g. Our study supports the association between LGA births and increased risks of maternal cancer, but this risk requires further investigation.

Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort.

BACKGROUND: Studies suggest that Wilms tumours (WT) are caused by underlying genetic (5%-10%) and epigenetic (2%-29%) mechanisms, yet studies covering both aspects are sparse. METHODS: We performed prospective whole-genome sequencing of germline DNA in Danish children diagnosed with WT from 2016 to 2021, and linked genotypes to deep phenotypes. RESULTS: Of 24 patients (58% female), 3 (13%, all female) harboured pathogenic germline variants in WT risk genes (FBXW7, WT1 and REST). Only one patient had a family history of WT (3 cases), segregating with the REST variant. Epigenetic testing revealed one (4%) additional patient (female) with uniparental disomy of chromosome 11 and Beckwith-Wiedemann syndrome (BWS). We observed a tendency of higher methylation of the BWS-related imprinting centre 1 in patients with WT than in healthy controls. Three patients (13%, all female) with bilateral tumours and/or features of BWS had higher birth weights (4780 g vs 3575 g; p=0.002). We observed more patients with macrosomia (>4250 g, n=5, all female) than expected (OR 9.98 (95% CI 2.56 to 34.66)). Genes involved in early kidney development were enriched in our constrained gene analysis, including both known (WT1, FBXW7) and candidate (CTNND1, FRMD4A) WT predisposition genes. WT predisposing variants, BWS and/or macrosomia (n=8, all female) were more common in female patients than male patients (p=0.01). CONCLUSION: We find that most females (57%) and 33% of all patients with WT had either a genetic or another indicator of WT predisposition. This emphasises the need for scrutiny when diagnosing patients with WT, as early detection of underlying predisposition may impact treatment, follow-up and genetic counselling.

Trajectories of maternal D-dimer are associated with the risk of developing adverse maternal and perinatal outcomes: A prospective birth cohort study.

OBJECTIVE: To assess the relationships of maternal D-dimer trajectories with the risk of developing adverse maternal and perinatal outcomes (AMPOs). METHODS: A prospective birth cohort study was conducted in China, and 7,095 women who had singleton birth were included. The latent class growth model was used to determine the maternal D-dimer trajectory. RESULTS: Three maternal D-dimer trajectories were identified: (1) slight increase (43.6%), (2) rapid rise (51.3%), (3) sustained high (5.1%). Compared to pregnant women with a slight increase in D-dimer trajectory, the risk of gestational diabetes mellitus, placenta previa, macrosomia, large for gestational age (LGA), and increased postpartum bleeding was significantly increased in those with a rapid rise trajectory (adjusted OR = 1.22, 2.00, 1.80, and 1.56, adjusted ß = 15.92 âˆ¼ 25.1 ml, respectively, P < 0.05), and women with a sustained high trajectory also demonstrated a relatively elevated risk of macrosomia and LGA (adjusted OR = 2.11 and 1.82, respectively, P < 0.05). While the odds of pregnancy-induced hypertension, low birth weight, and small for gestational age in pregnant women with the rapid rise D-dimer trajectory and fetal distress in those with sustained high trajectory exhibited a reduction (adjusted OR = 0.62, 0.38, 0.54, and 0.64, respectively, P < 0.05). CONCLUSION: This study highlights the influence of inappropriate maternal D-dimer trajectories on the risk of AMPOs.

Obstetrical and neonatal outcomes of cardio-facio-cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation.

We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio-facio-cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records. We identified 43 individuals with pathogenic variants in BRAF (81%), MEK1 (14%), or MEK2 (5%) genes. The median age was 8.5 years. Hyperemesis gravidarum, gestational diabetes, gestational hypertension, and preeclampsia occurred in 5/43 (12%), 4/43 (9%), 3/43 (7%), and 3/43 (7%) of pregnancies, respectively. Second and third trimester ultrasound abnormalities included polyhydramnios, macrocephaly, macrosomia, and renal and cardiac abnormalities. Delivery occurred via spontaneous vaginal, operative vaginal, or cesarean delivery in 15/42 (36%), 7/42 (16%), and 20/42 (48%), respectively. Median gestational age at delivery was 37 weeks and median birth weight was 3501 grams. Germline pathogenic vaiants had mutiple congenital consequences including polyhydramnios, renal and cardiac abnormalities, macrosomia, and macrocephaly on second and third trimester ultrasound. Elevated rates of operative delivery and neonatal complications were also noted. Understanding and defining a prenatal phenotype may improve prenatal prognostic counseling and outcomes.

Fetal Macrosomia and Postpartum Hemorrhage in Latin American and Caribbean Region: Systematic Review and Meta-analysis / Macrossomia fetal e hemorragia pós-parto na região da América Latina e Caribe: Revisão sistemática e metanálise

Abstract Objective To determine the association between fetal macrosomia (FM) and postpartum hemorrhage (PPH) in Latin American and Caribbean (LAC) women. Data Sources Studies evaluating the association between FM and PPH (≥ 500 ml) and severe PPH (≥ 1,000 ml) until November 4, 2021, indexed in CINHAL, Scopus, Embase, Cochrane Library, MEDLINE, LILACS, and SciELO. Selection of Studies Inclusion criteria were cohort and case-control studies that provided the number of PPH and FM cases. Exclusion criteria were studies lacking information about the number of cases, with a population of women who were not from LAC; published in a language other than English, Spanish, or Portuguese, and with a different design. Data Collection Data extraction was performed independently by two authors, and discrepancies were resolved with a third author. Data regarding FM and PPH cases were retrieved. Data Synthesis Of the 1,044 articles evaluated, 5 studies were included, from 6 different countries: Argentina and Uruguay (multi-country), West Indies, Antigua and Barbuda, French Guyana, and Suriname. The pooled odds ratio (OR) for FM and PPH in the meta-analysis (five studies) was 2.10 (95% confidence interval [CI]: 1.79-2.47; I2: 0%), with estimates within this 95% CI in the sensitivity analysis. The combined OR for severe PPH (3 studies) was 1.61 (95% CI: 0.40-6.48; I2: 91.89%), showing high heterogeneity. Conclusion There was a positive association between FM and PPH in the LAC, increasing the risk of the presence of this event 2-fold. The high heterogeneity of the studies that measured severe PPH does not allow drawing conclusions about the estimates obtained.

Resumo Objetivo Determinar a associação entre macrossomia fetal (FM) e hemorragia pós-parto (HPP) em mulheres da América Latina e Caribe (ALC). Fontes de dados Estudos avaliando a associação entre FM e HPP (≥ 500 ml) e HPP grave (≥ 1.000 ml) até 4 de novembro de 2021, indexados no CINHAL, Scopus, Embase, Biblioteca Cochrane, MEDLINE, LILACS e SciELO. Seleção de estudos Os critérios de inclusão foram estudos de corte e caso-controle que forneceram o número de casos de HPP e FM. Os critérios de exclusão foram estudos sem informação sobre o número de casos, com uma população de mulheres que não eram da ALC; publicado em um idioma diferente do inglês, espanhol ou português e com um design diferente. Coleta de dados A extração de dados foi realizada independentemente por dois autores, as discrepâncias foram resolvidas com um terceiro autor. Os dados relativos aos casos de FM e HPP foram recuperados. Síntese dos dados Dos 1.044 artigos avaliados, foram incluídos 5 estudos, de 6 países diferentes: Argentina e Uruguai (multipaíses), Índias Ocidentais, Antígua e Barbuda, Guiana Francesa e Suriname. O odds ratio agrupado (OR) para FM e HPP na meta-análise (cinco estudos) foi de 2,10 (intervalo de confiança de 95% [IC]: 1,79-2,47; I2: 0%), com estimativas dentro deste IC de 95% no análise sensitiva. O OR combinado para HPP grave (3 estudos) foi de 1,61 (95% CI: 0.40-6.48; I2: 91.89%), mostrando alta heterogeneidade. Conclusão Houve associação positiva entre FM e HPP na ALC, aumentando em 2 vezes o risco da presença desse evento. A alta heterogeneidade dos estudos que mediram a HPP grave não permite tirar conclusões sobre as estimativas obtidas.

Prontidão para via oral, aleitamento materno e diabetes mellitus gestacional: estudo caso-controle / Readiness for way oral, breastfeeding and gestational diabetes mellitus: a case-control study

RESUMO Objetivo verificar a prontidão para via oral e aleitamento materno em recém-nascidos de mães diagnosticadas com diabetes mellitus gestacional (DMG). Métodos estudo observacional, analítico, quantitativo, do tipo caso-controle. Para avaliação da sucção não nutritiva, foi utilizado o Protocolo de Prontidão do Prematuro para Início da Alimentação por Via Oral - POFRAS e, para avaliação do desempenho em seio materno, o Protocolo de Acompanhamento Fonoaudiológico - Aleitamento Materno. A amostra foi estratificada em dois grupos, sendo o grupo experimental composto por recém-nascidos de mães diagnosticadas com DMG e o grupo-controle, por recém-nascidos de mães hígidas. Para a análise estatística, foram utilizados os testes Mann-Whitney, Shapiro Wilk e t de Student. Resultados a amostra total foi composta por 46 recém-nascidos, sendo 21 do grupo experimental e 25 do grupo-controle. Observou-se p<0,05 na comparação entre os grupos nas seguintes variáveis: oscilação do estado de consciência, hipotonia global, reflexo de procura débil, menos de cinco sucções por pausa na avaliação da sucção não nutritiva, pega em seio, adormecimento após iniciar sucção e posicionamento mãe-bebê. Conclusão recém-nascidos de mães diagnosticadas com DMG apresentaram maior dificuldade na prontidão para via oral e na prática do aleitamento materno nas primeiras 72 horas de vida, comparados aos filhos de mães hígidas.

ABSTRACT Purpose to verify the readiness for oral feeding and breastfeeding in newborns of mothers diagnosed with gestational diabetes mellitus (GDM). Methods observational, analytical, quantitative case-control study. For the evaluation of non-nutritive sucking, the PROFAS protocol was used and for the evaluation of performance at the mother's breast, the protocol of Speech Therapy - Breastfeeding. The sample was stratified into two groups, the experimental group, composed of newborns of mothers diagnosed with GDM, and the control group, with newborns of healthy mothers. For statistical analysis, the Mann-Whitney, Shapiro Wilk and Student's t tests were used. Results the total sample consisted of 46 newborns, 21 from the experimental group and 25 from the control group. P<0.05 was observed in the comparison between the groups in the variables: oscillation in the state of consciousness, global hypotonia, weak search reflex, less than five suctions per pause in the assessment of non-nutritive sucking, holding on to the breast, falling asleep after starting suction and mother-infant positioning. Conclusion newborns of mothers diagnosed with GDM had greater difficulty in readiness for oral feeding and in the practice of breastfeeding in the first 72 hours of life, compared to children of healthy mothers.

Variables maternas relacionadas con la condición trófica al nacer / Maternal variables related to the trophic condition at birth

RESUMEN Introducción: El crecimiento y desarrollo prenatal tiene su expresión en el peso al nacer, que adquiere gran importancia por su relación con la morbilidad y mortalidad en cualquier etapa de la vida. Objetivo: Identificar las asociaciones de variables maternas con la condición trófica del recién nacido. Métodos: Se realizó un estudio descriptivo, en tres áreas de salud del municipio Santa Clara, en el periodo comprendido de enero 2013 a diciembre 2020. De una población de 6035 recién nacidos se seleccionó una muestra aleatoria de 2454. De los libros de genética se obtuvo la información de variables maternas y del neonato. Se aplicaron las pruebas no paramétricas de independencia basada en la distribución chi cuadrado y Kruskal Wallis en el análisis estadístico. Resultados: A excepción de la edad, las variables estudiadas mostraron relación con la condición trófica al nacer. El estado nutricional deficiente fue más frecuente en nacimientos pequeños y el obeso en los grandes. En nacimientos grandes se observó mayores porcentajes de gestantes con riesgo de diabetes gestacional. Los trastornos hipertensivos, la anemia, la infección del tracto urinario, la sepsis vaginal y el hábito de fumar se presentaron en mayores porcentajes en gestantes cuyos recién nacidos fueron pequeños. Conclusiones: De las variables estudiadas el riesgo de diabetes gestacional y los trastornos hipertensivos mostraron la mayor fuerza de asociación con la condición trófica al nacer.

ABSTRACT Introduction: prenatal growth and development have their expression in birth weight, which acquires great importance due to its relationship with morbidity and mortality at any stage of life. Objective: to identify the associations of maternal variables with the trophic condition of the newborn. Methods: a descriptive study was carried out in three health areas from Santa Clara municipality between January 2013 and December 2020. A random sample of 2,454 was selected from a population of 6,035 newborns. Information on maternal and newborn variables was obtained. Non-parametric tests of independence based on the Chi-square distribution and Kruskal Wallis were applied in the statistical analysis. Results: the variables studied showed a relationship with the trophic condition at birth, except for age. Poor nutritional status was more frequent in small births and obesity in large ones. In large births, higher percentages of pregnant women at risk of gestational diabetes were observed. Hypertensive disorders, anemia, urinary tract infection, vaginal sepsis and smoking were present in higher percentages in pregnant women whose newborns were small. Conclusions: from the studied variables, the risk of gestational diabetes and hypertensive disorders showed the strongest association with the trophic status at birth.

Gestational Diabetes Mellitus and High Triglyceride Levels Mediate the Association between Pre-Pregnancy Overweight/Obesity and Macrosomia: A Prospective Cohort Study in Central China.

The purpose of this study is to investigate whether the link between pre-pregnancy overweight/obesity and risk of macrosomia is mediated by both gestational diabetes mellitus (GDM) and high maternal triglyceride (mTG) levels. This prospective study finally included 29,415 singleton term pregnancies. The outcome of interest was macrosomia (≥4000 g). High mTG levels were denoted as values ≥90th percentile. GDM was diagnosed using a standard 75 g 2 h oral glucose tolerance test. The mediation analysis was conducted using log-binomial regression while controlling for maternal age, education, parity, gestational weight gain, gestational hypertension, smoking, drinking and infant sex. Overall, 15.9% of pregnant women were diagnosed with GDM, and 4.3% were macrosomia. Mediation analysis suggested that overweight had a total effect of 0.009 (95% CI, 0.006-0.013) on macrosomia, with a direct effect of 0.008 (95% CI, 0.004-0.012) and an indirect effect of 0.001 (95% CI, 0.001-0.002), with an estimated proportion of 11.1% mediated by GDM and high mTG levels together. Furthermore, we also discovered a total effect of obesity on macrosomia of 0.038 (95% CI, 0.030-0.047), consisting of a direct effect of 0.037 (95% CI, 0.028-0.045) and an indirect effect of 0.002 (95% CI, 0.001-0.002), with an estimated proportion of 5.3% mediated by GDM and high mTG levels combined. Both GDM and high mTG levels enhanced the risk of macrosomia independently and served as significant mediators in the relationship between pre-pregnancy overweight/obesity and macrosomia.

Predicting risk of postpartum haemorrhage during the intrapartum period in a general obstetric population.

OBJECTIVE: To develop and validate (both internally and externally) a prediction model examining a combination of risk factors in order to predict postpartum haemorrhage (PPH) in a general obstetric Irish population of singleton pregnancies. STUDY DESIGN: We used data from the National Maternal and Newborn Clinical Management System (MN-CMS), including all singleton deliveries at Cork University Maternity Hospital (CUMH), Ireland during 2019. We defined PPH as an estimated blood loss of ≥ 1000 ml following the birth of the baby. Multivariable logistic regression with backward stepwise selection was used to develop the prediction model. Candidate predictors included maternal age, maternal body mass index, parity, previous caesarean section, assisted fertility, gestational age, fetal macrosomia, mode of delivery and history of PPH. Discrimination was assessed using the area under the receiver operating characteristic curve (ROC) C-statistic. We used bootstrapping for internal validation to assess overfitting, and conducted a temporal external validation using data from all singleton deliveries at CUMH during 2020. RESULTS: Out of 6,077 women, 5,807 with complete data were included in the analyses, and there were 270 (4.65%) cases of PPH. Four variables were considered the best combined predictors of PPH, including parity (specifically nulliparous), macrosomia, mode of delivery (specifically operative vaginal delivery, emergency caesarean section and prelabour caesarean section), and history of PPH. These predictors were used to develop a nomogram to provide individualised risk assessment for PPH. The original apparent C-statistic was 0.751 (95% CI: 0.721, 0.779) suggesting good discriminative performance. There was minimal optimism adjustment to the C-statistic after bootstrapping, indicating good internal performance (optimism adjusted C-statistic: 0.748). Results of external validation were comparable with the development model suggesting good reproducibility. CONCLUSIONS: Four routinely collected variables (parity, fetal macrosomia, mode of delivery and history of PPH) were identified when predicting PPH in a general obstetric Irish population of singleton pregnancies. Use of our nomogram could potentially assist with individualised risk assessment of PPH and inform clinical decision-making allowing those at highest risk of PPH be actively managed.