The impact of reference growth standards on small- and large-for-gestational age outcomes among pregnancies conceived by fresh and frozen embryo transfers.

Objective: To describe differences in the frequency of small-for-gestational age (SGA) and large-for-gestational age (LGA) driven by different birth weight curves in assisted reproductive technology (ART)-conceived pregnancies. Design: Retrospective cohort study. Setting: Single academic medical center. Patients: Singleton live births between the gestational ages of 36 weeks and 0 days and 42 weeks and 6 days from fresh or frozen embryo transfer (ET). Interventions: None. Main Outcome Measures: SGA (<10th percentile) and LGA (>90th percentile) classified by Fenton, INTERGROWTH-21, World Health Organization, Duryea, and Oken curves. Results: The median birth weight and gestational age at birth among fresh ET pregnancies were 3,289g (interquartile range [IQR], 2,977-3,600g) and 39.4 (IQR, 38.6-40.3) weeks, respectively, and those among frozen ET pregnancies were 3,399g (IQR, 3,065-3,685g) and 39.4 (IQR, 38.7-40.1) weeks, respectively. The frequencies of SGA neonates using each birth weight standard ranged from 5.8% to 13.4% for fresh ET and from 3.5% to 8.7% for frozen ET. Those of LGA neonates ranged from 5.3% to 14.3% for fresh ET and from 6.6% to 21.2% for frozen ET. Conclusion: The frequency of SGA and LGA neonates among ART-conceived gestations is partially driven by the birth weight standard. Selecting an appropriate standard that best reflects the patient population is critical to quantifying the risk of ART-conceived pregnancies.

The impact of impaired intrauterine growth on male fertility: A systematic review and meta-analysis.

BACKGROUND: Adverse intrauterine environment was believed to have deleterious effects on the gonadal function. However, the association between impaired intrauterine growth and fertility in adult males has not been established. OBJECTIVES: To compare the reproductive rates of males born small for gestational age (SGA), with low birth weight (LBW) or very low birth weight (VLBW) with control groups. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed to search PubMed, Web of Science, Cochrane Library, and Embase databases from inception to June 16, 2023. Cohort studies investigating the reproductive rates of males born SGA, with LBW or VLBW were included. A random or fixed effects model was used for different exposures. RESULTS: A total of 10 studies out of 3,801 records were included. Males born SGA showed a higher risk of infertility than the control group (odds ratio, OR = 0.91, 95% confidence interval, 95% CI 0.89-0.93, p = 0.000). The reproductive rates of individuals born with LBW or VLBW were lower than the control group (OR = 0.86, 95% CI 0.78-0.94, p = 0.001; OR = 0.57, 95% CI 0.40-0.81, p = 0.002, respectively). Participants were further divided into two age groups of 18-35 and 35-45 years. In both subgroups, the reproductive rates were lower in males born SGA, with LBW or VLBW compared with controls. Sensitivity analysis showed the robustness of the pooled estimates among LBW and VLBW. CONCLUSION: In summary, SGA, LBW, and VLBW were associated with a higher risk of male infertility in both early and middle adulthood. Achieving optimal intrauterine growth would be helpful to prevent male infertility.

Association between risk of infant death and birth-weight z scores according to gestational age: A nationwide study using the Finnish Medical Birth Register.

OBJECTIVE: To investigate the association between infant mortality and birth weight using estimated fetal weight (EFW) versus birth-weight charts, by gestational age (GA). METHODS: This nationwide population-based study used data from the Finnish Medical Birth Register from 2006 to 2016 on non-malformed singleton live births at 24-41+6 weeks of gestation (N = 563 630). The outcome was death in the first year of life. Mortality risks by birth-weight z score, defined as a continuous variable using Marsál's EFW and Sankilampi's birth-weight charts, were assessed using generalized additive models by GA (24-27+6, 28-31+6, 32-36+6, 37-38+6, 39-41+6 weeks). We calculated z score thresholds associated with a two- and three-fold increased risk of infant death compared with newborns with a birth weight between 0 and 0.675 standard deviations. RESULTS: The z score thresholds (with corresponding centiles in parentheses) associated with a two-fold increase in infant mortality were: -3.43 (<0.1) at 24-27+6 weeks, -3.46 (<0.1) at 28-31+6 weeks, -1.29 (9.9) at 32-36+6 weeks, -1.18 (11.9) at 37-38+6 weeks, and - 1.34 (9.0) at 39-41+6 weeks according to the EFW chart. These values were - 2.43 (0.8), -2.62 (0.4), -1.34 (9.0), -1.37 (8.5), and - 1.43 (7.6) according to the birth-weight chart. CONCLUSION: The association between birth weight and infant mortality varies by GA whichever chart is used, suggesting that different thresholds for the screening of growth anomalies could be used across GA to identify high-risk newborns.

Preeclampsia and neonatal outcomes in pregnancies with maternal congenital heart disease: A nationwide cohort study from Norway.

INTRODUCTION: The prevalence of congenital heart disease (CHD) among women of reproductive age is rising. We aimed to investigate the risk of preeclampsia and adverse neonatal outcomes in pregnancies of mothers with CHD compared to pregnancies of mothers without heart disease. MATERIAL AND METHODS: In a nationwide cohort of pregnancies in Norway 1994-2014, we retrieved information on maternal heart disease, the course of pregnancy, and neonatal outcomes from national registries. Comparing pregnancies with maternal CHD to pregnancies without maternal heart disease, we used Cox regression to estimate the adjusted hazard ratio (aHR) for preeclampsia and log-binomial regression to estimate the adjusted risk ratio (aRR) for adverse neonatal outcomes. The estimates were adjusted for maternal age and year of childbirth and presented with 95% confidence intervals (CIs). RESULTS: Among 1 218 452 pregnancies, 2425 had mild maternal CHD, and 603 had moderate/severe CHD. Compared to pregnancies without maternal heart disease, the risk of preeclampsia was increased in pregnancies with mild and moderate/severe maternal CHD (aHR1.37, 95% CI 1.14-1.65 and aHR 1.62, 95% CI 1.13-2.32). The risk of preterm birth was increased in pregnancies with mild maternal CHD (aRR 1.33, 95% CI 1.15-1.54) and further increased with moderate/severe CHD (aRR 2.49, 95% CI 2.03-3.07). Maternal CHD was associated with elevated risks of both spontaneous and iatrogenic preterm birth. The risk of infants small-for-gestational-age was slightly increased with mild maternal CHD (aRR 1.12, 95% CI 1.00-1.26) and increased with moderate/severe CHD (aRR 1.63, 95% CI 1.36-1.95). The prevalence of stillbirth was 3.9 per 1000 pregnancies without maternal heart disease, 5.6 per 1000 with mild maternal CHD, and 6.8 per 1000 with moderate/severe maternal CHD. Still, there were too few cases to report a significant difference. There were no maternal deaths in women with CHD. CONCLUSIONS: Moderate/severe maternal CHD in pregnancy was associated with increased risks of preeclampsia, preterm birth, and infants small-for-gestational-age. Mild maternal CHD was associated with less increased risks. For women with moderate/severe CHD, their risk of preeclampsia and adverse neonatal outcomes should be evaluated together with their cardiac risk in pregnancy, and follow-up in pregnancy should be ascertained.

Inflammatory markers in relation to maternal lifestyle and adverse pregnancy outcomes in twin pregnancies.

It is well known that inflammatory markers play an important role in the development and maintenance of healthy pregnancies. However, the literature regarding inflammation in relation to lifestyle and adverse pregnancy outcomes in twin pregnancies is remarkably uncovered. Therefore, this study aimed at evaluating the concentration of inflammatory markers in dried capillary blood spot samples from 523 women with twin pregnancies, included at a median gestational age of 21+1 weeks. The relationship between inflammatory markers and maternal lifestyle (current smoking status and pre-pregnancy body mass index) in addition to adverse pregnancy outcomes (preeclampsia, gestational diabetes mellitus, and small for gestational age) was analyzed. The study showed that active smoking at inclusion was associated with an elevated concentration of interleukin-8. Furthermore, maternal obesity was associated with an elevated concentration of C-reactive protein and monocyte chemoattractant protein-1. Analysis of the data showed no statistically significant variations in the concentration of the assessed inflammatory markers for neither preeclampsia, gestational diabetes mellitus, nor small for gestational age. The current study promotes future research on the pathophysiology of twin pregnancies in relation to adverse pregnancy outcomes, as the literature within the area remains scarce.

A Comparison of Obstetric Outcomes in Antiphospholipid Syndrome Among Pregnant Women With Systemic Lupus Erythematosus.

Objective The aim of this study was to evaluate the maternal and perinatal outcomes in systemic lupus erythematosus (SLE) women with antiphospholipid syndrome (APS). Methods This retrospective case-control study was conducted among pregnant women with SLE with and without APS. Group A included SLE patients with APS, whereas group B included pregnant SLE women without APS. Data were expressed as mean ± standard deviation (SD). Frequency and percentage were computed for categorical data. The chi-square test was used to analyze the difference between categorical data. Results Out of 125 cases of SLE, APS was found in 72 (57.6%) women. Almost 95.8% of patients were on treatment (aspirin and enoxaparin) in group A. Preterm delivery (31.89±7.36 versus 34.46±4.97; p=0.021) and termination of pregnancy (18.1% [13/72] versus 5.7% [3/53]; p=0.04) were statistically significant in group A. Among these terminations, second-trimester intrauterine death is found to be more in group A (SLE with APS) (16.7% [12/72]) as compared to group B (SLE without APS) (5.7% [3/53]) with a p-value of 0.05. Perinatal outcomes including NICU admissions (39% [23/59] versus 24% [12/50]; p=0.071) and neonatal death (12.3% [7/57]; p=0.015) were also found to be statistically significant between the two groups. Conclusion APS with SLE is associated with adverse pregnancy outcomes such as preterm birth, termination of pregnancy due to second-trimester fetal loss, more NICU admission, and neonatal deaths when compared to the control group. Hence, pregnancies with APS with SLE require vigilant monitoring and frequent follow-ups to ensure a positive pregnancy outcome.

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

The search for blood biomarkers that indicate risk of adverse neurodevelopmental outcomes in fetal growth restriction.

Fetal growth restriction (FGR) impacts 5%-10% of pregnancies and is associated with increased risk of mortality and morbidity. Although adverse neurodevelopmental outcomes are observed in up to 50% of FGR infants, a diagnosis of FGR does not indicate the level of risk for an individual infant and these infants are not routinely followed up to assess neurodevelopmental outcomes. Identifying FGR infants at increased risk of adverse neurodevelopmental outcomes would greatly assist in providing appropriate support and interventions earlier, resulting in improved outcomes. However, current methods to detect brain injury around the time of birth lack the sensitivity required to detect the more subtle alterations associated with FGR. Blood biomarkers have this potential. This systematic review assessed the current literature on blood biomarkers for identifying FGR infants at increased risk of adverse neurodevelopmental outcomes at >12 months after birth. Four databases were searched from inception to 22 February 2024. Articles were assessed for meeting the inclusion criteria by two reviewers. The quality of the included article was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. A summary of findings is presented as insufficient articles were identified for meta-analysis. Excluding duplicates, 1,368 records were screened with only 9 articles considered for full text review. Only one article met all the inclusion criteria. Quality assessment indicated low risk of bias. Both blood biomarkers investigated in this study, neuron specific enolase and S100B, demonstrated inverse relationships with neurodevelopmental assessments at 2 years. Four studies did not meet all the inclusion criteria yet identified promising findings for metabolites and cytokines which are discussed here. These findings support the need for further research and highlight the potential for blood biomarkers to predict adverse outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369242, Identifier CRD42022369242.

Placental pathology lesions: International Society for Ultrasound In Obstetrics And Gynecology vs. Society for Maternal-Fetal Medicine Fetal growth restriction definitions.

BACKGROUND: Research on the definition of fetal growth restriction has focused on predicting adverse perinatal outcomes. A significant limitation of this approach is that the individual outcomes of interest could be related to the condition and the treatment. Evaluation of outcomes that reflect the pathophysiology of fetal growth restriction may overcome this limitation. OBJECTIVE: To compare the diagnostic performance of the fetal growth restriction definitions established by the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine to predict placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome. STUDY DESIGN: In this retrospective cohort study of singleton pregnancies, the International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine guidelines were used to identify pregnancies with fetal growth restriction and a corresponding control group. The primary outcome was the prediction of placental histopathological findings associated with placental insufficiency, defined as lesions associated with maternal vascular malperfusion. A composite adverse neonatal outcome (i.e., umbilical artery pH≤7.1, Apgar score at 5 minutes ≤4, neonatal intensive care unit admission, hypoglycemia, respiratory distress syndrome requiring mechanical ventilation, intrapartum fetal distress requiring expedited delivery, and perinatal death) was investigated as a secondary outcome. Sensitivity, specificity, positive and negative predictive values, and the areas under the receiver-operating-characteristics curves were determined for each fetal growth restriction definition. Logistic regression models were used to assess the association between each definition and the studied outcomes. A subgroup analysis of the diagnostic performance of both definitions stratifying the population in early and late fetal growth restriction was also performed. RESULTS: Both societies' definitions showed a similar diagnostic performance as well as a significant association with the primary (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 3.01 [95% confidence interval 2.42, 3.75]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.85 [95% confidence interval 2.31, 3.51]) and secondary outcomes (International Society for Ultrasound in Obstetrics and Gynecology adjusted odds ratio 1.95 [95% confidence interval 1.56, 2.43]; Society for Maternal-Fetal Medicine adjusted odds ratio 2.12 [95% confidence interval 1.70, 2.65]). Furthermore, both fetal growth restriction definitions had a limited discriminatory capacity for placental histopathological findings of maternal vascular malperfusion and the composite adverse neonatal outcome (area under the receiver-operating-characteristics curve International Society for Ultrasound in Obstetrics and Gynecology 0.63 [95% confidence interval 0.61, 0.65], 0.59 [95% confidence interval 0.56, 0.61]; area under the receiver-operating-characteristics Society for Maternal-Fetal Medicine 0.63 [95% confidence interval 0.61, 0.66], 0.60 [95% confidence interval 0.57, 0.62]). CONCLUSIONS: The International Society for Ultrasound in Obstetrics and Gynecology and the Society for Maternal-Fetal Medicine fetal growth restriction definitions have limited discriminatory capacity for placental histopathological findings associated with placental insufficiency and a composite adverse neonatal outcome.

Role of ghrelin in promoting catch-up growth and maintaining metabolic homeostasis in small-for-gestational-age infants.

Small-for-gestational age (SGA) has been a great concern in the perinatal period as it leads to adverse perinatal outcomes and increased neonatal morbidity and mortality, has an impact on long-term health outcomes, and increases the risk of metabolic disorders, cardiovascular, and endocrine diseases in adulthood. As an endogenous ligand of the growth hormone secretagotor (GHS-R), ghrelin may play an important role in regulating growth and energy metabolic homeostasis from fetal to adult life. We reviewed the role of ghrelin in catch-up growth and energy metabolism of SGA in recent years. In addition to promoting SGA catch-up growth, ghrelin may also participate in SGA energy metabolism and maintain metabolic homeostasis. The causes of small gestational age infants are very complex and may be related to a variety of metabolic pathway disorders. The related signaling pathways regulated by ghrelin may help to identify high-risk groups of SGA metabolic disorders and formulate targeted interventions to prevent the occurrence of adult dwarfism, insulin resistance-related metabolic syndrome and other diseases.

Health-related quality of life and problem behaviour after GH cessation in adults born SGA: a 12-year follow-up study.

CONTEXT: Long-term data regarding HRQoL and problem behaviour in adults born SGA who were treated with GH during childhood are lacking. OBJECTIVE: To investigate longitudinal changes in HRQoL and problem behaviour in adults born SGA during 12 years after cessation of childhood GH-treatment (SGA-GH), and compare these with 3 control groups at age around 30 years. PARTICIPANTS: 176 SGA-GH adults and 3 untreated age-matched control groups: 50 born SGA with short stature (SGA-S), 77 born SGA with spontaneous catch-up growth to normal height (SGA-CU) and 99 born appropriate-for-gestational-age with normal height (AGA). MAIN OUTCOME MEASURES: HRQoL and problem behavior were assessed using TNO-AZL Adults Quality of Life questionnaire (TAAQoL) and Adolescent Behavior Check List (ABCL) at 6 months, 2, 5 and 12 years after GH-cessation. Data at 12-years after GH-cessation were compared with 3 control groups. RESULTS: During 12 years after GH-cessation, HRQoL remained similar on 9 subscales in SGA-GH adults, but decreased on 3 subscales (gross motor functioning, pain, sleep). Externalizing problem behaviour decreased significantly and internalizing problem behaviour tended to decrease. SGA-GH and SGA-S adults had similar HRQoL and problem behaviour. SGA-GH adults had, compared to AGA adults, similar HRQoL on 7 subscales, lower HRQoL on 5 subscales and more internalizing and externalizing problem behaviour. All SGA adults had lower HRQoL and more internalizing problem behaviour than AGA adults. Adult height associated negatively with externalizing problem behaviour, but the influence was small. CONCLUSIONS: During 12 years after GH-cessation, HRQoL remained mostly similar and problem behaviour decreased in SGA-GH adults. SGA-GH and SGA-S adults had similar HRQoL and problem behaviour. All SGA adults had lower HRQoL and more internalizing problem behaviour than AGA adults.

Serum Folate, Red Blood Cell Folate, and Zinc Serum Levels Are Related with Gestational Weight Gain and Offspring's Birth-Weight of Adolescent Mothers.

BACKGROUND: Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension. OBJECTIVE: The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City. RESULTS: In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age. CONCLUSIONS: Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.

Impact of cord entanglement on perinatal outcome.

OBJECTIVE: To evaluate the impact of umbilical cord entanglement around various fetal organs on perinatal outcomes. STUDY DESIGN: A retrospective population-based study of all deliveries between 1988 and 2016 at a tertiary medical center. Immediate perinatal outcomes of newborns with and without cord entanglement were compared. RESULTS: The prevalence of any cord entanglement in our population was 16.62 % (45,312 cases out of 272,713 deliveries during the study period). Cord entanglement was found to be significantly associated with antepartum fetal death (OR = 2.13, 95 % CI 1.77-2.57, p < 0.001) and one-minute Apgar score less than 7 (OR = 1.21, 95 % CI 1.16-1.27, p < 0.001). There was no association between cord entanglement and small for gestational age (SGA) babies. CONCLUSION: Cord entanglement is associated with antepartum fetal death, but not with SGA.

Perinatal outcomes after in-utero exposure to beta-blockers in women with heart disease: Data from the ESC EORP registry of pregnancy and cardiac disease (ROPAC).

BACKGROUND: Beta-blockers are commonly used drugs during pregnancy, especially in women with heart disease, and are regarded as relatively safe although evidence is sparse. Differences between beta-blockers are not well-studied. METHODS: In the Registry of Pregnancy And Cardiac disease (ROPAC, n = 5739), a prospective global registry of pregnancies in women with structural heart disease, perinatal outcomes (small for gestational age (SGA), birth weight, neonatal congenital heart disease (nCHD) and perinatal mortality) were compared between women with and without beta-blocker exposure, and between different beta-blockers. Multivariable regression analysis was used for the effect of beta-blockers on birth weight, SGA and nCHD (after adjustment for maternal and perinatal confounders). RESULTS: Beta-blockers were used in 875 (15.2%) ROPAC pregnancies, with metoprolol (n = 323, 37%) and bisoprolol (n = 261, 30%) being the most frequent. Women with beta-blocker exposure had more SGA infants (15.3% vs 9.3%, p < 0.001) and nCHD (4.7% vs 2.7%, p = 0.001). Perinatal mortality rates were not different (1.4% vs 1.9%, p = 0.272). The adjusted mean difference in birth weight was -177 g (-5.8%), the adjusted OR for SGA was 1.7 (95% CI 1.3-2.1) and for nCHD 2.3 (1.6-3.5). With metoprolol as reference, labetalol (0.2, 0.1-0.4) was the least likely to cause SGA, and atenolol (2.3, 1.1-4.9) the most. CONCLUSIONS: In women with heart disease an association was found between maternal beta-blocker use and perinatal outcomes. Labetalol seems to be associated with the lowest risk of developing SGA, while atenolol should be avoided.

The association of physical activity during pregnancy with birthweight extremes: A scoping review.

OBJECTIVES: Birthweight (BW) indicates newborn health and is a risk factor for development of chronic diseases later in life. The aim was to investigate whether or not prenatal physical activity (PA) influences BW extremes and how PA influences BW extremes in those diagnosed with pregnancy-related diseases. DESIGN: We performed a scoping review. METHODS: Searches were completed on five databases and studies identified were uploaded to Covidence. RESULTS: Across the five databases 3114 studies were identified and after screening, 69 of these studies were used for the final review. Of the 61 studies that considered low BW (LBW)/small for gestational age (SGA) infants, the majority of results (69 %) indicated that PA during pregnancy had no significant impact on LBW or SGA infants. In addition, 11 % of studies reported a significant decrease in the prevalence of LBW infants, however two studies (3 %) reported a significant increase in LBW or SGA infants, likely relating to individuals with high body mass index and poor adherence to PA. Of the 41 studies that did report LGA/macrosomia, 34 % reported that PA significantly reduced the prevalence of higher BW infants. One study reported the association between meeting exercise recommendations and reducing the odds of LGA infants in those with pregnancy-related diseases. CONCLUSIONS: We provide evidence on the association of prenatal PA with BW extremes. It is suggested that prenatal PA does not increase the risk of delivering LBW/SGA infants and may reduce the prevalence of large BW infants. Further research is needed to confirm these relationships and explain their underlying mechanisms.

Maternal serum biomarkers of placental insufficiency at 24-28 weeks of pregnancy in relation to the risk of delivering small-for-gestational-age infant in Sylhet, Bangladesh: a prospective cohort study.

BACKGROUND: Small-for-gestational-age (SGA), commonly caused by poor placentation, is a major contributor to global perinatal mortality and morbidity. Maternal serum levels of placental protein and angiogenic factors are changed in SGA. Using data from a population-based pregnancy cohort, we estimated the relationships between levels of second-trimester pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PlGF), and serum soluble fms-like tyrosine kinase-1 (sFlt-1) with SGA. METHODS: Three thousand pregnant women were enrolled. Trained health workers prospectively collected data at home visits. Maternal blood samples were collected, serum aliquots were prepared and stored at -80℃. Included in the analysis were 1,718 women who delivered a singleton live birth baby and provided a blood sample at 24-28 weeks of gestation. We used Mann-Whitney U test to examine differences of the median biomarker concentrations between SGA (< 10th centile birthweight for gestational age) and appropriate-for-gestational-age (AGA). We created biomarker concentration quartiles and estimated the risk ratios (RRs) and 95% confidence intervals (CIs) for SGA by quartiles separately for each biomarker. A modified Poisson regression was used to determine the association of the placental biomarkers with SGA, adjusting for potential confounders. RESULTS: The median PlGF level was lower in SGA pregnancies (934 pg/mL, IQR 613-1411 pg/mL) than in the AGA (1050 pg/mL, IQR 679-1642 pg/mL; p < 0.001). The median sFlt-1/PlGF ratio was higher in SGA pregnancies (2.00, IQR 1.18-3.24) compared to AGA pregnancies (1.77, IQR 1.06-2.90; p = 0.006). In multivariate regression analysis, women in the lowest quartile of PAPP-A showed 25% higher risk of SGA (95% CI 1.09-1.44; p = 0.002). For PlGF, SGA risk was higher in women in the lowest (aRR 1.40, 95% CI 1.21-1.62; p < 0.001) and 2nd quartiles (aRR 1.30, 95% CI 1.12-1.51; p = 0.001). Women in the highest and 3rd quartiles of sFlt-1 were at reduced risk of SGA delivery (aRR 0.80, 95% CI 0.70-0.92; p = 0.002, and aRR 0.86, 95% CI 0.75-0.98; p = 0.028, respectively). Women in the highest quartile of sFlt-1/PlGF ratio showed 18% higher risk of SGA delivery (95% CI 1.02-1.36; p = 0.025). CONCLUSIONS: This study provides evidence that PAPP-A, PlGF, and sFlt-1/PlGF ratio measurements may be useful second-trimester biomarkers for SGA.

Maternal rest improves growth in small-for-gestational-age fetuses (<10th percentile).

BACKGROUND: Optimal management of fetuses diagnosed as small for gestational age based on an estimated fetal weight of <10th percentile represents a major clinical problem. The standard approach is to increase fetal surveillance with serial biometry and antepartum testing to assess fetal well-being and timing of delivery. Observational studies have indicated that maternal rest in the left lateral position improves maternal cardiac output and uterine blood flow. However, maternal bed rest has not been recommended based on the results of a randomized clinical trial that showed that maternal rest does not improve fetal growth in small-for-gestational-age fetuses. This study was conducted to revisit this question. OBJECTIVE: This study aimed to determine whether maternal bed rest was associated with an increase in the fetal biometric parameters that reflect growth after the diagnosis of a small-for-gestational-age fetus. STUDY DESIGN: A retrospective study was conducted on fetuses who were diagnosed as small for gestational age because of an estimated fetal weight of <10th percentile for gestational age. The mothers were asked to rest in the left lateral recumbent position. Fetal biometry was performed 2 weeks after the diagnosis. All fetuses before entry into the study had a previous ultrasound that demonstrated an estimated fetal weight of >10th percentile. To assess the response to bed rest, the change in fetal biometric parameters (estimated fetal weight, head circumference, abdominal circumference, and femur length) after the recommendation of bed rest was computed for 2 periods: (1) before the diagnosis of a weight of <10th percentile vs at the time of diagnosis of a weight of <10th percentile and (2) at the time of diagnosis of a weight of <10th percentile vs 2 weeks after maternal bed rest. For repeated measures, proportions were compared using the McNemar test, and percentile values were compared using the Kruskal-Wallis test. A P value of <.05 was considered significant. To describe changes in the estimated fetal weight without bed rest, 2 control groups in which the mothers were not placed on bed rest after the diagnosis of a small-for-gestational-age fetus were included. RESULTS: A total of 265 fetuses were observed before and after maternal bed rest. The following were observed in this study: (1) after 2 weeks of maternal rest, 199 of 265 fetuses (75%) had a fetal weight of >10th percentile; (2) the median fetal weight percentile increased from 6.8 (interquartile range, 4.4-8.4) to 18.0 (interquartile range, 9.5-29.5) after 2 weeks of bed rest; (3) similar trends were noted for the head circumference, abdominal circumference, and femur length. In the groups of patients who were not asked to be on bed rest, a reassignment to a weight of >10th percentile at a follow-up examination only occurred in 7 of 37 patients (19%) in the Texas-Michigan group and 13 of 111 patients (12%) in the Colorado group compared with the bed rest group (199/265 [75%]) (P<.001). CONCLUSION: Patients who were prescribed 2 weeks of bed rest after the diagnosis of a fetal weight of <10th percentile had an increase in weight of >10th percentile in 199 of 265 fetuses (75%). This increase in fetal weight was significantly higher than that in the 2 control groups in which bed rest was not prescribed. This observation suggests that bed rest improves fetal growth in a subset of patients.

Is the sFlt-1/PlGF ratio efficient in predicting adverse neonatal outcomes in small-for-gestational-age newborns? A prospective observational multicenter cohort study.

Introduction: Fetuses with growth abnormalities are at an increased risk of adverse neonatal outcomes. The aim of this study was to investigate if placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), or the sFlt-1/PlGF ratio were efficient predictive factors of adverse neonatal outcomes in small-for-gestational-age (SGA) newborns. Methods: A prospective observational multicenter cohort study was performed between 2020 and 2023. At the time of the SGA fetus diagnosis, serum angiogenic biomarker measurements were performed. The primary outcome was an adverse neonatal outcome, diagnosed in the case of any of the following: <34 weeks of gestation: mechanical ventilation, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge; ≥34 weeks of gestation: Neonatal Intensive Care Unit hospitalization, mechanical ventilation, continuous positive airway pressure, sepsis, necrotizing enterocolitis, intraventricular hemorrhage grade III or IV, and neonatal death before discharge. Results: In total, 192 women who delivered SGA newborns were included in the study. The serum concentrations of PlGF were lower, leading to a higher sFlt-1/PlGF ratio in the adverse outcome group. No significant differences in sFlt-1 levels were observed between the groups. Both PlGF and sFlt-1 had a moderate correlation with adverse neonatal outcomes (PlGF: R - 0.5, p < 0.001; sFlt-1: 0.5, p < 0.001). The sFlt-1/PlGF ratio showed a correlation of 0.6 (p < 0.001) with adverse outcomes. The uterine artery pulsatility index (PI) and the sFlt-1/PlGF ratio were identified as the only independent risk factors for adverse outcomes. An sFlt-1/PlGF ratio of 19.1 exhibited high sensitivity (85.1%) but low specificity (35.9%) in predicting adverse outcomes and had the strongest correlation with them. This ratio allowed the risk of adverse outcomes to be assessed as low with approximately 80% certainty. Discussion: The sFlt-1/PlGF ratio seems to be an efficient predictive tool in adverse outcome risk assessment. More studies on large cohorts of SGA-complicated pregnancies with and without preeclampsia are needed to develop an optimal and detailed formula for the risk assessment of adverse outcomes in SGA newborns.

Pregnancy Outcomes After Bariatric Surgery: Importance of Maternal Ferritin on Birth Weight.

PURPOSE: The risks carried by pregnancy after bariatric surgery (BS) include small-for-gestational age (SGA) newborn and prematurity. However, the underlying mechanisms are not yet fully understood in pregnant women after BS. MATERIAL AND METHODS: This single-center retrospective observational cohort study includes all women with a first and single pregnancy after BS who completed at least one clinical and biological nutritional assessment during pregnancy between 2010 and 2016. The quarterly biological assessment comprised blood count, ferritin, calcium, 25OH vitamin D, parathyroid hormone, fasting glucose, albumin, prealbumin, vitamin A, vitamin B12, folic acid, and zinc. RESULTS: Among 120 pregnancies analysed, two-thirds underwent gastric bypass (Roux-en-Y and one-anastomosis) and one-third a restrictive procedure (adjustable gastric band or sleeve gastrectomy). The median [Q1-Q3] preoperative BMI was 43.8 [41.1-47.7] kg/m2 and the mean age at pregnancy was 32.6 ± 5.3 years. Weight loss and time from surgery to pregnancy were 35.1 ± 15.4 kg and 2.9 [1.3-4.5] years, respectively. Ten women (8%) gave birth prematurely, and 22 newborns (19%) were SGA. Univariate analysis shows that ferritin was significantly higher in mothers with SGA than in those without SGA (35.5 [22.3-69.5] vs. 15 [10-32] ng/ml) at third trimester of pregnancy. Women who received pre-pregnancy nutritional assessment seemed less likely to give birth to a SGA newborn (32% vs. 54%, p = 0.07). CONCLUSION: Iron supplementation should be carefully prescribed and closely monitored during pregnancy in women who have undergone BS.

The Relationship of Preterm and Small for Gestational Age with Child Cognition During School-Age Years.

BACKGROUND: Children born preterm and/or small for gestational age (SGA) are at increased risk of poor cognitive outcomes, particularly in low and middle-income countries (LMICs). OBJECTIVES: This study aimed to examine the cognitive and academic deficits during the school-age years in children born preterm or SGA compared with those in children born term adequate for gestational age (AGA) in rural Vietnam. METHODS: Children born to women in a preconception micronutrient supplementation trial in Vietnam were classified into 3 groups: preterm AGA (n =138), term SGA (n =169), and term AGA (n = 1134). Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children, measuring 4 domains [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) scores] and full-scale intelligence quotient (FSIQ) at 6-7 and 10-11 y. Academic achievement was assessed with mathematic and language tests. Analysis of variance and multiple regression models were used to analyze differences in cognitive function and academic achievement at 6-7 and 10-11 y by birth phenotypes. RESULTS: Compared with term AGA children, those born SGA had lower cognitive scores at both 6-7 y (VCI, -2.3; PRI, -3.7; PSI -2.1; and FSIQ, -2.9) and 10-11 y (VCI, -3.7; PRI, -3.5; WMI, -2.7; PSI, -1.9; and FSIQ, -3.9). Children born SGA also had poorer academic achievement with lower language (5.3) and mathematic (2.5) scores. Adjustments for maternal factors and home environment attenuated the associations, but the differences in VCI, PRI, FSIQ, and language at 10-11 y remained significant. There were no differences in cognitive function and academic achievement between children born preterm and AGA. CONCLUSIONS: Our findings highlight the enduring association of birth phenotype on cognitive functioning and academic achievement during the school years, despite adjustments for maternal education and family environment. Further research is needed to implement effective interventions to improve birth outcomes and optimize child health and development in LMICs. The trial was registered at clinicaltrials.gov as NCT01665378 (URL: https://clinicaltrials.gov/ct2/show/NCT01665378).