Birth Weight Percentile Research Articles

#2740 Pregnancy outcomes in patients with IgA nephropathy and the impact of pregnancy on the renal disease

Abstract Background and Aims IgA nephropathy (IgAN), the predominant primary glomerulonephritis in adults,, frequently affects women in childbearing age. There is a dearth of information about the impact of pregnancy on the outcome in IgAN especially in the Indian population where it is known to have an aggressive disease phenotype. This retrospective cohort study examines pregnancy outcomes in women with biopsy-proven IgAN and the impact on renal outcome. Method In a retrospective cohort study, we assessed the medical records of women in child bearing age (18-40 years) diagnosed with biopsy proven primary IgAN from 2012-2022. Patients with end stage kidney disease (ESKD) at the time of biopsy and/or at time of conception and those who had undergone kidney transplantation were excluded. Maternal (pre-eclampsia, relapse, renal disease progression, etc.) and fetal outcomes (neonatal death, preterm delivery, intra-uterine growth retardation-IUGR, etc.) were recorded. Relapse was defined as increase in proteinuria to ≥1 g/day during pregnancy and renal disease progression as >40% sustained decline in eGFR and/or ESKD. Results Of 75 women assessed, 25 were lost to follow up. 34 did not conceive after biopsy. 20 pregnancies were documented in 14 patients. Three (15%) were medically terminated, 7 (35%) resulted in spontaneous abortions, and 10 (50%) culminated in live births. There was one neonatal death. 6/20(30%) pregnancies occurred while the patient was on ACEi/ARBs of which 5 pregnancies resulted in live births. 7/10 (70%) births were premature, 5 being moderate preterm (34-37 weeks) and 2 late preterm (32-34 weeks). IUGR below the 5th percentile affected 7/10(70%) of births. The mode of delivery was evenly split between vaginal (5, 50%) and Caesarian (5, 50%). From a maternal perspective, preeclampsia affected 3/10 (30%) patients. 5/10(50%) patients who delivered had a relapse during pregnancy with 2 developing nephrotic range proteinuria. 4 of them receiving steroids during pregnancy. All relapsed patients had persistent proteinuria >1 g/day postpartum. In 2 (20%) pregnancies, relapse developed during immediate post-partum period. In 4 patients, eGFR decreased by > 40 percent compared to their baseline (at biopsy) following the pregnancy. Conclusion Pregnancy is associated with adverse maternal and fetal outcomes in women with IgA nephropathy. eGFR, estimated glomerular filtration rate. IUGR, Intra-uterine growth restriction (based on birth weight percentile, adjusted for gender and gestational age). *Serum creatine of one patient during pregnancy is not available, analysis is done using values of other 9 patients. **Urine Protein of one patient is not available at the latest follow-up, analysis is done using values of 9 other patients.

Minerals and trace elements in pregnancy in women with previous bariatric surgery consequences on maternal and foetal health

BackgroundBariatric surgery (BS) may decrease the risk of these obesity-related complications; however, due to its effect on nutrient intake and absorption, it can also have adverse consequences on maternal and foetal health. The aim of this study is to describe the evolution of electrolytes and trace elements serum levels throughout pregnancy after BS, according to the surgical technique and to evaluate the effect of nutritional deficiencies on the risk of maternal-foetal complications. MethodsThis is a retrospective observational study of the clinical evolution and maternal-foetal complications in a group of women with pregnancies that occurred after BS. Clinical evolution during pregnancy, body weight, and plasma electrolytes, vitamins, and trace elements, as well as their influence on maternal-foetal outcomes were evaluated. Composite neonatal variable (CNV) was defined to evaluate unfavourable foetal outcome. Published reference values for micronutrients during pregnancy have been used. ResultsThe study includes data on 164 singleton pregnancies in 91 women. A hundred and twenty-seven pregnancies got to full term. The average birth weight was 2966 (546) g., 26.8% < P10 and 13.8% < P3 of a reference population. New-born of gestations after malabsorptive bariatric surgery had a higher risk of having a percentile of birth weight < P3. Plasma electrolytes, trace elements and vitamins throughout pregnancy showed differences depending on the surgical technique, with lower haemoglobin, ferritin, calcium, zinc, copper, vitamin A and vitamin E in the malabsorptive techniques. A high percentage of deficiency was observed, especially in the third trimester (Hb < 11 g/dl: 31.8%; ferritin < 30 mg/ml: 85.7%; zinc < 50 μg/dl: 32.4%, vitamin D < 30 ng/ml: 75.5% and < 20 ng/ml: 53.3%). A decreased plasma copper in the first trimester or zinc in the third trimester were associated with a lower percentile of new-born birth weight. A higher risk of CNV was observed in predominant malabsorptive BS and in pregnancies that had presented at least one vitamin D level lower than 20 ng/ml throughout pregnancy (30.4% vs. 7.1%, p=0.018). ConclusionsTrace elements and vitamin deficiencies are common in pregnant women after bariatric surgery, especially of iron, zinc, and vitamin D. These deficiencies might negatively affect foetal development. Further studies are needed to better define the role of micronutrients in maternal-foetal health after bariatric surgery.

Impact of bariatric surgery on maternal gestational weight gain and pregnancy outcomes in women with obesity: A population-based cohort study from Qatar.

Bariatric surgery is performed in obese women of reproductive age to help achieve a healthy prepregnancy weight to reduce the complications associated with obesity in pregnancy. However, these procedures can impact maternal nutrition and gestational weight gain (GWG). This study evaluates the maternal and neonatal outcomes in women with prepregnancy bariatric surgery and determines the impact on GWG. This study included 24 weeks gestation or more pregnancies, with a maternal BMI at delivery of 30 kg/m2 or more. It was categorized into two groups based on whether they had prepregnancy bariatric surgery (exposed) or not (unexposed). The outcomes included gestational diabetes (GDM), gestational hypertension (GHT), mode of delivery, preterm birth (PTB), GWG, birthweight (BW) and customized BW centiles, low birthweight (LBW), congenital anomalies, and admission to the neonatal intensive unit (NICU). Categorization was also done based on the adequacy of GWG (low, adequate, and excess). A total of 8,323 women were included in the study, 194 of whom had prepregnancy bariatric surgery. After adjusting for confounders, the exposed group had a mean GWG 1.33 kg higher than the unexposed group (95% CI 0.55-2.13, p=0.001). The exposed group had higher odds of PTB (aOR 1.78, 95% CI 1.16-2.74, p=0.008), CD (aOR 6.52, 95% CI 4.28-9.93, p<0.001), LBW in term babies (aOR 2.60, 95% CI 1.34-5.03, p=0.005), congenital anomalies (aOR 2.64, 95% CI 1.21-5.77, p=0.015), low APGAR score (aOR 3.75, 95% CI 1.12-12.5, p=0.032) and 80.4g lesser birthweight (95% CI -153.0, -5.8; p=0.034). More women in the low GWG category had LBW babies (28.6% versus 6.7% in the high GWG group, p=0.033), lowest mean BW and median BW centiles (2775 grams versus 3289 grams in the high GWG group, p=0.004 and 57.5% versus 74.5% in the high GWG group, p=0.040, respectively). The findings of this study highlight differences in perinatal outcomes such as preterm birth, low birth weight, congenital anomalies, cesarean deliveries, and gestational weight gain between post-bariatric women and controls. These insights can help inform the planning and provision of appropriate maternity care to enhance patient safety and outcomes. The results of this study can also guide the counseling of reproductive age-group women who are planning to undergo bariatric surgery.

Nitric oxide donor increases umbilical vein blood flow and fetal oxygenation in fetal growth restriction. A pilot study

IntroductionTo evaluate the maternal and fetal hemodynamic effects of treatment with a nitric oxide donor and oral fluid in pregnancies complicated by fetal growth restriction. Methods30 normotensive participants with early fetal growth restriction were enrolled. 15 participants were treated until delivery with transdermal glyceryl trinitrate and oral fluid intake (Treated group), and 15 comprised the untreated group. All women underwent non-invasive assessment of fetal and maternal hemodynamics and repeat evaluation 2 weeks later. ResultsIn the treated group, maternal hemodynamics improved significantly after two weeks of therapy compared to untreated participants. Fetal hemodynamics in the treated group showed an increase in umbilical vein diameter by 18.87 % (p < 0.01), in umbilical vein blood flow by 48.16 % (p < 0.01) and in umbilical vein blood flow corrected for estimated fetal weight by 30.03 % (p < 0.01). In the untreated group, the characteristics of the umbilical vein were unchanged compared to baseline. At the same time, the cerebro-placental ratio increased in the treated group, while it was reduced in the untreated group, compared to baseline values. The treated group showed a higher birthweight centile (p = 0.03) and a lower preeclampsia rate (p = 0.04) compared to the untreated group. DiscussionThe combined therapeutic approach with nitric oxide donor and oral fluid intake in fetal growth restriction improves maternal hemodynamics, which becomes more hyperdynamic (volume-dominant). At the same time, in the fetal circuit, umbilical vein flow increased and fetal brain sparing improved. Although a modest sample size, there was less preeclampsia and a higher birthweight suggesting beneficial maternal and fetal characteristics of treatment.

Validity of a Delphi consensus definition of growth restriction in the newborn for identifying neonatal morbidity

BackgroundSmall-for-gestational age (SGA) is defined as a birthweight below a birthweight-percentile threshold, usually the 10th percentile, with the 3rd or 5th percentile used to identify severe SGA. SGA is used as a proxy for growth restriction in the newborn, but SGA newborns can be physiologically small and healthy. This definition also excludes growth restricted newborns who have weights above the 10th percentile. To address these limits, a Delphi study developed a new consensus definition of growth restriction in the newborn based on neonatal anthropometric and clinical parameters, but it has not been evaluated. ObjectivesTo assess the prevalence of growth restriction in the newborn according to the Delphi consensus definition and to investigate associated morbidity risks compared to definitions of SGA using birthweight-percentile thresholds. Study designData come from the 2016 and 2021 French National Perinatal Surveys which include all births ≥22 weeks and/or with birthweights ≥500 grams in all maternity units in France over a one-week period. Data are collected from medical records and interviews with mothers after the delivery. The study population included 23,897 liveborn singleton births. The Delphi consensus definition of growth restriction was birthweight <3rd percentile or at least 3 of the following criteria: birthweight, head circumference or length <10th percentile, antenatal diagnosis of growth restriction or maternal hypertension. A composite of neonatal morbidity at birth, defined as five-minute Apgar score <7, cord arterial pH <7.10, resuscitation and/or neonatal admission, was compared using the Delphi definition and usual birthweight-percentile thresholds for defining SGA using the following birthweight percentile groups: <3rd, 3rd-4th and 5th-9th percentiles. Relative risks were adjusted (aRR) for maternal characteristics (age, parity, body mass index, smoking, educational level, pre-existing hypertension and diabetes, and study year) and then for the consensus definition and birthweight percentile groups. Multiple imputation by chained equations was used to impute missing data. Analyses were carried out in the overall sample and among term and preterm newborns separately. Results4.9% (95% confidence intervals (CI): 4.6-5.2) of newborns were identified with growth restriction, of whom 29.7% experienced morbidity, yielding a aRR of 2.5 (95% CI: 2.2-2.7) compared to newborns without growth restriction. Compared to birthweight ≥10th percentile, morbidity risks were higher for low birthweight percentiles (<3rd aRR=3.3 (95%CI: 3.0-3.7), 3rd-4th RR=1.4 (95%CI:1.1-1.7), 5th-9th RR=1.4, (95%CI:1.2-1.6)). In adjusted models including the definition of growth restriction and birthweight percentile groups and excluding birthweights <3rd percentile, which are included in both definitions, morbidity risks remained higher for birthweights at the 3rd-4th percentile (aRR=1.4, 95% CI: 1.1-1.7) and 5th-9th percentile (aRR= 1.4, 95%CI: 1.2-1.6), but not for the Delphi definition of growth restriction (aRR= 0.9, 95%CI: 0.7-1.2). Similar patterns were found for term and preterm newborns. ConclusionThe Delphi consensus definition of growth restriction did not identify more newborns with morbidity than definitions of SGA based on birthweight percentiles. These findings illustrate the importance of evaluating the results of Delphi consensus studies before their adoption in clinical practice.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study

BackgroundThe aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. MethodsThis was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000–2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests.Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. FindingsThe final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0·19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13·2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0·74%), with the highest rate (19·6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7·59% livebirths), with the peak incidence occurring in the <1st centile category (12·3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10–90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. InterpretationAlthough the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently “appropriately grown” (i.e., birthweight 10th - 90th centile). FundingNational Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women’s Health Foundation – Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

Maternal positional therapy for fetal growth and customised birth weight centile benefit in a Bayesian reanalysis of a double-blind, sham-controlled, randomised clinical trial

ObjectivesTo update the Ghana PrenaBelt Trial’s (GPT) primary outcome data with the latest fetal growth standard and reanalyse it. To estimate the posterior probability, under various clinically relevant prior probabilities,...

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study

BackgroundWith the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth...

Dose-response effect of prenatal alcohol exposure on perinatal outcomes.

A better understanding of the effects of lower levels of prenatal alcohol exposure (PAE), as a common exposure, is needed. The goal of this study was to examine the effects of mild-moderate PAE and episodic binge drinking on perinatal outcomes. The data were obtained from three prospective cohorts with a combined sample of 281 participants: 125 with PAE and 156 without PAE. Alcohol-related measures included the Alcohol Use Disorders Identification Test, timeline follow-back questionnaires (covering the periconceptional period, mid-gestation, and late gestation), and biomarkers. Absolute alcohol per day (AAD) and per drinking day (AADD), number of binge episodes, and maximum number of drinks in a 24-h period were estimated. Perinatal outcomes included gestational age and anthropometric measures. Data were analyzed using correlation and multivariable regression analysis. Among women with PAE, average alcohol consumption across the periconceptional period and pregnancy was 0.37 oz ± 0.74 AA/day (~5 drinks/week). After adjusting for tobacco co-exposure and sociodemographic characteristics, significant associations between all alcohol measures and gestational age at delivery were observed, including cumulative measures of AAD (β = -0.58; 95% CI: -0.98; -0.17) and AADD (β = -0.58; 95% CI: -0.90; -0.26) during pregnancy and the periconceptional period. A significant association between the maximum number of drinks in a 24-h period and birth length percentile (β = -0.70; 95% CI: -1.36; -0.04) was observed in the final model. PAE was associated with lower birth weight percentile in univariate analyses only. Results of this study demonstrate a negative association between mild-moderate PAE and episodic binge drinking with gestational age at delivery and birth length percentile after controlling for other factors. Robust negative effects of PAE, including in the periconceptional period before pregnancy recognition, on duration of gestation highlight the need for primary prevention efforts aimed at PAE in persons of reproductive age.

Macular Curvature in Adults Born Preterm With and Without ROP: Results from the Gutenberg Prematurity Eye Study.

This study investigated the effects of prematurity and retinopathy of prematurity (ROP) as well as the associations of the ocular geometry with macular curvature in adults. The Gutenberg Prematurity Eye Study is a retrospective cohort study of preterm and full-term participants aged 18 to 52years with a prospective ophthalmologic examination. The main outcome measure was the macular curvature in the central foveal optical coherence tomography (OCT) scan and its associations with gestational age (GA), birth weight and birth weight percentile, ROP occurrence, ROP treatment, and other perinatal factors were evaluated in univariable and multivariable linear regression analyses. Furthermore, a second model assessed the association of ocular geometry with macular curvature. In the present study, 550 eyes of 284 adults born preterm and 277 eyes of 139 adults born full-term were examined (aged = 28.7 ± 8.7years, 240 female subjects). In multivariable analyses for perinatal parameters, ROP treatment (B = -52.44, P = 0.023) and maternal smoking during pregnancy (B = 26.41, P = 0.019) showed an association with macular curvature. Regarding ocular geometric parameters, posterior segment length (B = 9.07, P < 0.001) and subfoveal choroidal thickness (B = -0.26, P < 0.001) were associated with macular curvature, central corneal thickness, anterior chamber depth, lens thickness, and foveal retinal thickness were not associated. Adults treated for ROP had relatively more negative curvature values compared to the full-term group, indicating a macular protrusion toward the vitreous cave. A thicker subfoveal choroidal thickness was associated with a flatter macular curvature, whereas a longer posterior segment length was associated with a steeper macular curvature indicating the characteristics of the myopic elongation of the eye.

Tumor Necrosis Factor Inhibitor Use Increases Birthweight in Pregnant Women With Rheumatoid Arthritis Independently of the Soluble Fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio.

To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt-1 (soluble Fms-like tyrosine kinase-1), PlGF (placental growth factor), or their impact on birthweight. sFlt-1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt-1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt-1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester-related variation in levels of sFlt-1 and PlGF, after correction for relevant confounders, the sFlt-1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt-1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54-26.29], P=0.79; sFlt-1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73-22.50], P=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P=0.03), and sFlt-1 displayed a negative correlation with birthweight (r=-0.462, P<0.001) and birthweight percentile (r=-0.332, P=0.008). In TNFi users, these correlations were absent. TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt-1/PlGF ratio. http://clinicaltrials.gov. Unique identifier: NCT01345071.

The sFlt-1/PlGF Ratio at 12, 24, and 32 Weeks Gestation in Twin Pregnancies as a Predictor of Placental Dysfunction.

Background: This study aims to assess the utility of the sFlt-1/PlGF ratio throughout pregnancy in predicting placental dysfunction and neonatal outcomes in twin pregnancies. Methods: Prospective study at a tertiary hospital. All pregnant women with a twin pregnancy who signed the informed consent were included. The sFlt-1/PlGF ratio was measured at 12, 24, and 32 weeks' gestation. Results: Seventy patients were included, and 30% developed placental dysfunction. Differences were found in the mean sFlt-1/PlGF ratios at week 32 (13.6 vs. 31.8, p = 0.007). Optimal cutoffs at 12, 24, and 32 weeks to identify patients who develop placental dysfunction were 32.5, 8.5, and 30.5, respectively, with ORs of 4.25 (1.13-20.69 95% IC; p = 0.044), 13.5 (3.07-67.90 95% IC; p = 0.001), 14.29 (3.59-66.84 95% IC; p < 0.001). The sFlt-1/PlGF ratio at 32 weeks was associated with gestational age at birth. The sFlt-1/PlGF ratio in weeks 24 and 32 had a statistically significant negative correlation with the birth weight percentile in both twins. Conclusions: The potential of the sFlt-1/PlGF ratio as a predictive tool for placental dysfunction in twin pregnancies is underscored.

Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth: the Rotterdam Periconception Cohort.

Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints β = 0.017, 95% CI [0.009; 0.025], bifurcation points β = 0.012, 95% CI [0.006; 0.018], crossing points β = 0.017, 95% CI [0.008; 0.025], vessel points β = 0.01, 95% CI [0.002; 0.008], and total vascular length β = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV β = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV β = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV β -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV β = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically. Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. Registered at the Dutch Trial Register (NTR6854).

Isolated fetal umbilical vein varix and the association with intrauterine fetal death and fetal growth restriction: A systematic review, meta-analysis, and nested retrospective cohort study.

To assess the risk of intrauterine fetal death (IUFD) and fetal growth restriction (FGR) in fetuses with an isolated fetal intra-abdominal umbilical vein varix (i-FIUVV). A retrospective cohort study combined with a systematic review and meta-analysis of the literature was performed. In the retrospective cohort study, all singleton fetuses with an i-FIUVV in the fetal medicine units of the Amsterdam UMC (between 2007 and 2023) were analyzed. The primary outcome measures were IUFD and FGR. The sample proportions of IUFD and FGR were depicted as risk percentages. The IUFD proportion was compared to the regional reference population and the FGR proportion was compared to the reported proportions in Europe. The secondary outcome measures were gestational age at diagnosis, initial and maximal FIUVV diameter, fetal monitoring in pregnancy, turbulent flow in the varix, thrombus formation in the varix, induction of labor, gestational age at birth, and birthweight centile. The proportion of fetuses with a birthweight below the 10th centile was compared with that of the regional reference population. The systematic review included all cases from eligible literature published between 2007 and 2023 supplemented by the data of our retrospective cohort study. In the systematic review and meta-analysis, the pooled proportions of IUFD and FGR were assessed in fetuses with i-FIUVV. The retrospective cohort included 43 singletons with an i-FIUVV. The IUFD risk was 0% [Confidence Interval, CI: 0%-8.2%], which did not differ significantly from 0.3% in the reference population, p=1.0. The risk of FGR was 16.3% [CI: 6.8%-30.7%] in the studied population, which is higher than the reported incidence of FGR in Europe ranging from 5%-10%. The proportion of fetuses with birthweights below the 10th centile was higher in our cohort compared with the reference population (23.3 vs. 9.9%, p<0.01). The systematic review included 12 articles, three abstracts, and our current cohort. In total, 513 cases with an i-FIUVV were included. The pooled risk was 0.4% [CI: 0.1%-1.7%] for IUFD and 5.2% [CI: 1.1%-21.3%] for FGR. The mean gestational age at birth did not exceed 39weeks in neither the cohort (38.7weeks) nor the pooled literature (37.6weeks). An i-FIUVV in singletons is not associated with an increased IUFD risk up to 39weeks of gestation but is possibly associated with FGR. The incidence of FGR in our cohort was higher than in the pooled literature (16.3% vs. 5%) but FGR definitions in the included studies varied. The proportion of birthweights below the 10th percentile in our cohort was significantly higher than in the reference group. Thus, based on these findings, we suggest conducting sonographic growth assessments while simultaneously assessing the i-FIUVV. No further monitoring and follow-up are indicated up to 39weeks of gestation. After 39weeks of gestation, data on fetuses with i-FIUVV and their outcomes are lacking.

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity

Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present. We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy. In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission). The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies withboth gestational diabetes and hypertensive disorders of pregnancycompared with unaffected pregnancies (adjusted odds ratio, 0.72 [95%confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001). Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity.

Improved estimation of the relationship between fetal growth and late stillbirth in the United States, 2014–15

In the United States the rate of stillbirth after 28 weeks’ gestation (late stillbirth) is 2.7/1000 births. Fetuses that are small for gestational age (SGA) or large for gestational age (LGA) are at increased risk of stillbirth. SGA and LGA are often categorized as growth or birthweight ≤ 10th and ≥ 90th centile, respectively; however, these cut-offs are arbitrary. We sought to characterize the relationship between birthweight and stillbirth risk in greater detail. Data on singleton births between 28- and 44-weeks’ gestation from 2014 to 2015 were extracted from the US Centers for Disease Control and Prevention live birth and fetal death files. Growth was assessed using customized birthweight centiles (Gestation Related Optimal Weight; GROW). The analyses included logistic regression using SGA/LGA categories and a generalized additive model (GAM) using birthweight centile as a continuous exposure. Although the SGA and LGA categories identified infants at risk of stillbirth, categorical models provided poor fits to the data within the high-risk bins, and in particular markedly underestimated the risk for the extreme centiles. For example, for fetuses in the lowest GROW centile, the observed rate was 39.8/1000 births compared with a predicted rate of 11.7/1000 from the category-based analysis. In contrast, the model-predicted risk from the GAM tracked closely with the observed risk, with the GAM providing an accurate characterization of stillbirth risk across the entire birthweight continuum. This study provides stillbirth risk estimates for each GROW centile, which clinicians can use in conjunction with other clinical details to guide obstetric management.

Maternal height, and ethnicity and birth weight: A retrospective cohort study of uncomplicated term vaginal deliveries in Malaysia.

Small for gestational age (SGA) and large for gestational age (LGA) are designations given to neonates based solely on birthweight, with no distinction made for maternal height. However, there is a possibility that maternal height is significantly correlated with neonatal birthweight, and if so, SGA and LGA cutoffs specific to maternal height may be a more precise and useful tool for clinicians. To explore this possibility, we analyzed the association between maternal height and ethnicity and neonate birthweight in women with low-risk, 37- to 40-week gestation, singleton pregnancies who gave birth vaginally between 2010 and 2017 (n = 354,488). For this retrospective cohort study, we used electronic obstetric records obtained from the National Obstetrics Registry in Malaysia. National Obstetric Registry (NOR) data were used to calculate the 10th and 90th birthweight percentiles for each maternal height group by gestational age and neonatal sex. Multiple linear regression models, adjusted for maternal age, weight, parity, gestational age, and neonatal sex, were used to examine the association between neonate birthweight and maternal ethnicity and height. The following main outcome measures were assessed: small for gestational age (<10th percentile), large for gestational age (>90th percentile), and birthweight. The median height was 155 cm (IQR, 152-159), with mothers of Chinese descent being the tallest (median (IQR): 158 cm (154-162)) and mothers of Orang Asli (Indigenous) descent the shortest (median (IQR): 151 cm (147-155)). The median birthweight was 3000 g (IQR, 2740-3250), with mothers of Malay and Chinese ethnicity and Others having, on average, the heaviest babies, followed by other Bumiputeras (indigenous) mothers, mothers of Indian ethnicity, and lastly, mothers of Orang Asli ethnicity. For infants, maternal age, height, weight, parity, male sex, and gestational age were positively associated with birthweight. Maternal height had a positive association with neonate birthweight (B = 7.08, 95% CI: 6.85-7.31). For ethnicity, compared with neonates of Malay ethnicity, neonates of Chinese, Indian, Orang Asli, and other Bumiputera ethnicities had lower birthweights. Birthweight increases with maternal height among Malaysians of all ethnicities. SGA and LGA cutoffs specific to maternal height may be useful to guide pregnancy management.

Placentae of small appropriately-grown-for-gestational-age neonates exhibit sexually dimorphic transcriptomic changes representative of placental insufficiency

IntroductionPrevious studies have reported that neonates less than the 25th BWC especially if they were male, were more likely to be associated with birth complications suggesting small neonates often identified as appropriately grown are at risk of adverse outcomes. We have questioned whether smaller neonates not typically categorized as “small for gestational age” may not reach their genetically determined growth due to placental insufficiency. MethodsRNA-Seq was performed on the Illumina NovaSeq 600 using term placentae from neonates that were less than the 10th birthweight centile (BWC) (n = 39), between the 10th and the 30th BWC (n = 15) or greater than the 30th BWC (n = 23). Bioinformatic analyses were conducted and statistical significance was assessed at a level of P < 0.05 for single comparisons or FDR <0.05 unless otherwise noted. ResultsGene set enrichment analysis revealed differences between BWC groups and in relation to the sex of the placenta. Genes associated with hypoxia, inflammatory responses, estrogen responsive genes, and androgen responsive genes were enriched (FDR <0.1) for in placentae of neonates <10th BWC regardless of sex and also in male placentae of neonates between the 10th-30th BWC. Female placenta of neonates between the 10th-30th BWC were comparable to placentae of neonates >30th BWC. DiscussionThese findings provide evidence that small male neonates may be at a greater risk of an adverse outcome than females due to changes in gene expression that are associated with placental dysfunction. The current data raises questions of whether placental pathology for smaller appropriately grown neonates should be scientifically and clinically examined in more depth.

Infant Mortality Categorized by Birth Weight Percentiles for Deliveries between 22 and 28 Weeks of Gestation.

Our objective was to describe infant mortality within 1 year of life according to gestational age and birth weight percentile in infants delivered between 22 and 28 weeks of gestation. This study was a retrospective cohort study based on publicly available U.S. birth certificate data linked to infant death data between 2014 and 2020. Maternal-neonate pairs of singleton live births between 220/7 and 286/7 weeks' gestation (vaginal or cesarean) were evaluated. We excluded infants with major fetal anomalies, chromosomal disorders, and birth weight outliers. Our primary outcome was infant mortality within 1 year of life. Individuals were categorized into eight sex-specific birth weight percentiles categories: less than the 3rd, 3rd-less than the 10th, 10th-less than the 25th, 25th-to less than the 50th, 50th-less than the 75th, 75th-to less than the 90th, 90th-less than the 97th, and 97th or higher. Of 27,014,444 individuals with live births from January 2014 to December 2020, 151,677 individuals who gave birth at 22 to 28 weeks of gestation were included in the study population. The mortality rate ranged from 4.2% for the 50th-less than the 75th percentiles at 28 weeks to 80.3% for the 3rd-less than the 10th percentile at 22 weeks. Using the 50th-less than the 75th birth weight percentile at each gestational age as a reference group, birth weight less than the 50th percentile was associated with increased mortality at all gestational ages in a dose-dependent manner. From 22 to 25 weeks of gestation, higher birth weight percentiles were associated with lower mortality, while the 97th or higher birth weight percentile was associated with increased mortality compared with the 50th-less than the 75th birth weight percentile at 26 to 28 weeks of gestation. The lower birth weight percentiles were associated with higher mortality across all gestational ages, but the association between higher birth weight percentiles and infant mortality exhibited an opposite pattern at 22 to 25 weeks as compared to later gestational age. · Birth weight ≥97th percentile was associated with increased infant mortality at 26 to 28 weeks.. · Higher birth weight percentiles were associated with a lower risk of mortality at 22 to 25 weeks.. · Lower birth weight percentiles were associated with a higher risk of mortality at 22 to 28 weeks..

Fetal Growth Restriction Leads to an Enlarged Cup-to-Disc Ratio in Adults Born at Full Term

PurposeThis study explores associations between fetal growth restriction or excessive fetal growth, along with perinatal factors on the optic nerve head morphology in adulthood. DesignRetrospective cohort study. MethodsThis retrospective cohort study involved a prospective ophthalmological examination of individuals born at full term (with a gestational age of ≥37 weeks) from 1969 to 2002. Each participant underwent non-mydriatic fundus camera photography to capture images of the optic discs, followed by manual measurements. The vertical cup-to-disc ratio (VCDR) and optic disc area were examined and analyzed in relation to the baby's birth weight relative to the gestational age. These categories included those with former moderate (birth weight percentile between the 3rd and <10th), severe SGA (below the 3rd percentile), normal (AGA, 10th-90th percentile), and moderately (birth weight >90th to 97th percentile) and severely (birth weight >97th percentile) large for gestational age (LGA) adults within the age range of 18 to 52 years. ResultsOverall, 535 eyes of 280 individuals (age 29.74±9.23 years, 144 females) born at full term were included. Multivariable analysis showed a significant association between a larger VCDR and the severe SGA group (B = 0.05, 95% CI 0.01-0.10; p = 0.02). In the univariable model, placental insufficiency was associated with VCDR (B=0.10, 95% CI 0.01-0.19; p=0.03). Other perinatal factors did not demonstrate an association with VCDR. Furthermore, there was an indication of an association suggesting a smaller optic disc area in individuals born moderately SGA at full term (B = -0.17, 95% CI -0.33- -0.001; p = 0.05). ConclusionThis study provides evidence that individuals born at-term with severe SGA have an increased VCDR, suggesting that fetal growth restriction has a lasting impact on optic disc morphology independent of prematurity throughout adulthood.