Fetal Growth Restriction Research Articles

Sex Differences in Impacts of Early Gestational and Peri-Adolescent Ozone Exposure on Lung Development in Rats: Implications for Later Life Disease in Humans

Air pollution exposure during pregnancy may affect fetal growth. Fetal growth restriction (FGR) is associated with reduced lung function in children that can persist into adulthood. Using an established model of asymmetrical FGR in Long-Evans rats, this study investigated sex differences in effects of early life ozone exposure on lung development and maturation. Adverse health effects for i) gestational exposure (with impacts on primary alveolarization), ii) peri-adolescent exposure (with impacts on secondary alveolarization), and iii) cumulative exposure across both periods were evaluated. Notably, female offspring were most affected by gestational ozone exposure, likely because of impaired angiogenesis and corresponding decreases in primary alveolarization. Females had diminished lung capacity, fewer mature alveoli, and medial hypertrophy of small and large pulmonary arteries. Males, especially FGR-prone offspring, were more affected by peri-adolescent ozone exposure. Males had increased ductal areas, likely due to disrupted secondary alveolarization. Altered lung development may increase risk of developing diseases, such as pulmonary arterial hypertension or chronic obstructive pulmonary disease. Pulmonary arterial hypertension disproportionately affects women. In the United States, chronic obstructive pulmonary disease prevalence is increasing, especially in women; and prevalence for both men and women is highest in urbanized areas. This investigation underlines the importance of evaluating results separately by sex, and provides biologic plausibility for later consequences of early-life exposure to ozone, a ubiquitous urban air pollutant.

Cook’s balloon versus dinoprostone for Labour induction of term pregnancies with fetal GROWth restriction: study protocol for a randomised controlled trial in tertiary maternity hospitals in Spain (COLIGROW study)

IntroductionFetal growth restriction (FGR) affects about 3%–5% of term pregnancies. If prenatally detected and anterograde umbilical artery flow is preserved (stage I), it is recommended to deliver at term (≥...

Pregnancy outcomes in patients with systemic lupus erythematosus compared to a high-risk tertiary cohort andtostandard population from the Austrian birth registry.

Women with systemic lupus erythematosus (SLE) have a higher risk for fetal and maternal complications. We aimed to investigate maternal and fetal complications in pregnant women with SLE compared to a high-risk pregnancy cohort (HR) from a tertiary university center and a standard-risk general population (SR) from the Austrian Birth Registry. In this retrospective data analysis, we compared the incidence of fetal/neonatal and maternal complications of pregnancies and deliveries of women with SLE to age, body mass index and delivery date-matched high-risk pregnancies from the same department, a progressive tertiary obstetric center and to a group of women, who represent pregnancies with standard obstetric risk from the Austrian Birth Registry. One hundred women with SLE were compared to 300 women with high-risk pregnancies and 207 039 women with standard-risk pregnancies. The incidence of composite maternal complications (preeclampsia, Hemolysis, Elevated Liver enzymes and Low Platelets [HELLP] syndrome, pregnancy-related hypertension, gestational diabetes mellitus, maternal death, thromboembolic events) was significantly higher in the SLE as compared to the SR group (28% vs. 6.28% SLE vs. SR, p = 0.001). There was no difference between the SLE and the HR groups (28% vs. 29.6% SLE vs. HR group, p = 0.80). The incidence of composite fetal complications (preterm birth before 37 weeks of gestation, stillbirths, birthweight less than 2500 g, fetal growth restriction, large for gestational age, admission to neonatal intensive care unit, 5-min Apgar <7) was also higher in the SLE than in the SR group (55% vs. 25.54% SLE vs. SR p < 0.001) while the higher incidence of adverse fetal outcome was detected in the HR than in the SLE group (55% vs. 75% SLE vs. HR group, p = 0.0005). Although composite fetal risk is higher in the SLE group than in the general population, it is still significantly lower as compared to high-risk pregnant women at a tertiary obstetric center. Prepregnancy counseling of women with SLE should put fetal and maternal risk in perspective, not only in relation to healthy, low risk cohorts, but also compared to mixed HR populations.

Syncytiotrophoblast-derived extracellular vesicles in fetal growth restriction

Syncytiotrophoblast-derived extracellular vesicles in fetal growth restriction

Abstract P207: Regulation of Fetal-Placental ACE and ACE2 in COVID-19 Exposed Pregnancies Compared to Hypertensive and Healthy Pregnancies

Introduction: Higher risks of preterm birth and fetal growth restriction are observed in COVID-19 pregnancies. The infection mechanism, linked to a potential depletion of the cardioprotective protein ACE2, which serves as a receptor for SARS-CoV-2, could pose additional risks for mothers and fetuses. An ACE2/ACE imbalance, favoring ACE, has been seen in hypertensive (HT) pregnancies and is linked to poor outcomes, including pre-eclampsia. This study aims to assess whether similar changes in ACE and ACE2 regulation in placentas and umbilical cord blood occur in COVID-19 compared to HT and healthy (Ctrl) pregnancies, and whether this imbalance is associated with impaired vascular structure. Methods: A retrospective cohort study recruited 77 pregnancies (25 COVID-19, 16 HT, 36 Ctrl) at Montreal Hospital Sacré-Coeur. Placental infarction was assessed in histological sections, umbilical cord fibrosis by Masson's trichrome staining, and placental ACE2 content by immunohistochemistry. ACE and ACE2 activity were measured by fluorometric assay in umbilical cord plasma. Data are presented as mean 95% CI. Linear regression was used for correlations, Kruskal-Wallis and Mann-Whitney tests for group comparisons. Results: Maternal age, gestational age, and the proportion of male/female fetuses were similar between groups. Ctrl group had lower rates of C-section delivery, obesity, and gestational diabetes compared to COVID-19 and HT pregnancies. Although ACE2 content in placentas was reduced in HT pregnancies, the COVID-19 group had significantly higher content compared to HT and Ctrl pregnancies (23.4 CI=20.4-26.4 vs. 15.5 CI=9.7-21.3 and 17.6 CI=15.1-20.1, respectively, p&lt;0.01). The ACE2/ACE activity ratio in cord blood was significantly reduced in COVID-19 and HT groups compared to Ctrl (3.1 CI=2.4-3.6, 2.5 CI=1.7-3.1, and 4.1 CI=3.5-4.8, p&lt;0.01), indicating an imbalance favoring ACE activity in HT and COVID-19 groups. The ACE2/ACE ratio negatively correlated with umbilical cord fibrosis (slope=-3.1 CI= -6.1 to -0.1, p=0.04) and was significantly lower in placentas with tissue infarction (2.5 CI=1.2-3.8 vs. 4.6 CI=3.8-5.3, p&lt;0.01). Conclusion: HT pregnancies have reduced ACE2 content and an ACE2/ACE activity imbalance in cord blood. COVID-19 pregnancies show a similar imbalance in cord blood but significantly higher ACE2 content in the placenta. This imbalance is associated with structural changes in fetal-placental vessels, suggesting a link to poor pregnancy outcomes.

Abstract MP30: The Role of CD20+ B cells in Mediating Hypertension in Preeclampsia during Pregnancy

Pre-eclampsia (PE), new-onset hypertension after the 20 th week of pregnancy alongside other organ dysfunction, endothelial dysfunction, and immune activation. We have previously shown that CD19+ B cell adoptive transfer causes a PE phenotype in athymic nude rats. CD19 is present on all B cells including plasma cells. CD20 is absent from plasma cells but is present on mature B2 and memory B cells. The objective of this study was to determine if CD20+ B cells, excluding plasma cells, cause maternal hypertension, fetal growth restriction, and endothelial dysfunction. Three hundred thousand placental CD20+ B Cells from normal pregnant (NP) or PE patients were isolated by magnetic separation and injected i.p. into nude athymic rats on gestational day (GD) 12. On GD18, carotid catheters were inserted. On GD19, mean arterial pressure (MAP) was measured and blood and tissues were collected. Preproendothelin (PPET) expression was quantified in kidney and placental tissues using RT-PCR. A student’s t-test was used for statistical analysis. Participants whose placental B cells were used in this study had similar age, pre-pregnancy BMI, and diastolic BP on admission. PE participants had elevated systolic BP at admission (135±4 vs 120±4 mmHg) and delivery (139±6 vs 124±3 mmHg) as well as diastolic BP at delivery (79±4 vs 68±2 mmHg). PE participants also had trending decreases in fetal weight (2621±323 vs 3202±102 g) and gestational age (36±1 vs 39±0 weeks) at delivery. MAP increased from 107±4 mmHg (n=8) in the NP recipient rats to 123±2 mmHg (n=8, p&lt;0.01) in the PE recipient rats. Pup and placental weights were unchanged following adoptive transfer. Renal PPET expression increased by 2.595±0.61 fold (ΔΔct) in PE recipient rats (n=7, p&lt;0.05) compared to NP recipient rats (n=7). Placental PPET expression was unchanged following adoptive transfer. CD20+ B cells from women with PE contribute to hypertension and endothelial dysfunction during pregnancy. This data supports the important role of B cells in the development of PE and improves our understanding of the population of B cells responsible for contribution to the disease.

Placental Sonomorphologic Appearance and Fetomaternal Outcome in Fontan Circulation.

Objectives: Pregnancies in women with Fontan circulation are on the rise, and they are known to imply high maternal and fetal complication rates. The altered hemodynamic profile of univentricular circulation affects placental development and function. This study describes placental sonomorphologic appearance and Doppler examinations and correlates these to histopathologic findings and pregnancy outcomes in women with Fontan circulation. Methods: A single-center retrospective analysis of pregnancies in women with Fontan circulation was conducted between 2018 and 2023. Maternal characteristics and obstetric and neonatal outcomes were recorded. Serial ultrasound examinations including placental sonomorphologic appearance and Doppler studies were assessed. Macroscopic and histopathologic findings of the placentas were reviewed. Results: Six live births from six women with Fontan physiology were available for analysis. Prematurity occurred in 83% (5/6 cases) and fetal growth restriction and bleeding events in 66% (4/6 cases) each. All but one placenta showed similar sonomorphologic abnormalities starting during the late second trimester, such as thickened globular shape, inhomogeneous echotexture, and hypoechoic lakes, resulting in a jelly-like appearance. Uteroplacental blood flow indices were within normal range in all women. The corresponding histopathologic findings were non-specific and consisted of intervillous and subchorionic fibrin deposition, villous atrophy, hypoplasia, or fibrosis. Conclusions: Obstetric and perinatal complication rates in pregnancies of women with Fontan circulation are high. Thus, predictors are urgently needed. Our results suggest that serial ultrasound examinations with increased awareness of the placental appearance and its development, linked to the Doppler sonographic results of the uteroplacental and fetomaternal circulation, may be suitable for the early identification of cases prone to complications.

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Association between serum hormone levels in early pregnancy and risk of hypertensive diseases of pregnancy in women undergoing assisted reproduction.

We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction. Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated. A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317pg/mL, P4: 64 vs 29ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients. P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR.

Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 (hIGF1). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth. The objective of this pilot study was to extend these studies to the pregnant nonhuman primate and develop a method for local delivery of nanoparticles to the placenta via maternal blood flow from the uterine artery. Nanoparticles containing hIGF1 plasmid driven by the placenta-specific PLAC1 promoter were delivered to a mid-gestation pregnant rhesus macaque via a catheterization approach that is clinically used for uterine artery embolization. Maternal-fetal interface, fetal and maternal tissues were collected four days post-treatment to evaluate the efficacy of hIGF1 treatment in the placenta. The uterine artery catheterization procedure and nanoparticle treatment was well tolerated by the dam and fetus through the four-day study period following catheterization. Nanoparticles were taken up by the placenta from maternal blood as plasmid-specific hIGF1 expression was detected in multiple regions of the placenta via in situ hybridization and qPCR. The uterine artery catheterization approach enabled successful delivery of nanoparticles to maternal circulation in close proximity to the placenta with no concerns to maternal or fetal health in this short-term feasibility study. In the future, this delivery approach can be used for preclinical evaluation of the long-term safety and efficacy of nanoparticle-mediated placental therapies in a rhesus macaque model.

NLRP3 and IL-18 Expression Increases in Cases of Fetal Growth Restriction

NLRP3 and IL-18 Expression Increases in Cases of Fetal Growth Restriction

A case of Breus’ mole that was diagnosed with sequential ultrasound observation after finding severe fetal growth restriction.

A case of Breus’ mole that was diagnosed with sequential ultrasound observation after finding severe fetal growth restriction.

Hematopoietically expressed (HEX) gene is a transcriptional regulator of placental angiogenesis in human fetal growth restriction; altering expression of its downstream target genes may improve vascular function.

Hematopoietically expressed (HEX) gene is a transcriptional regulator of placental angiogenesis in human fetal growth restriction; altering expression of its downstream target genes may improve vascular function.

A case of fetal growth restriction with intraplacental hematoma and intraplacental umbilical cord

A case of fetal growth restriction with intraplacental hematoma and intraplacental umbilical cord

Abstract 68: Soluble FMS-Like Tyrosine Kinase 1 induces Vascular Endothelial Dysfunction in Pregnant Female Mice

Preeclampsia (PE) is a hypertensive disorder of pregnancy clinically characterized by hypertension and increased risk of fetal growth restriction. Elevated levels of anti-angiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) is a well-known hallmark of PE. In addition, emerging clinical evidence indicates that vascular endothelial dysfunction is a mediator of PE. Although these two facets of PE are associated, whether sFlt-1 is a crucial mediator in endothelial dysfunction in PE is unknown. We previously showed that the placenta-derived hormone leptin, whose levels characteristically increase in PE patients, induces the features of PE in pregnant mice, notably endothelial dysfunction. Novel preliminary data also shows that sFlt-1 induces an increase in placental leptin production, however, what remains to be explored is whether this pathway mediates endothelial dysfunction in PE pregnant mice. Therefore, we hypothesize that in pregnant mice, sFlt-1 induces vascular endothelial dysfunction via increasing leptin production. We bred BALB/c female mice for timed pregnancy (12-14 wk old). On gestational day (GD)11, pregnant females were implanted with subcutaneous (sc.) minipumps containing either sFlt-1 (1.2 µg/day, n=5) or saline (n=6). Uterine artery resistance index (UARI) was measured at GD17 via Doppler ultrasound. At GD18, vascular reactivity was measured in 2nd-order mesenteric arteries by wire myography. Our data showed that sFlt-1 increased UARI compared to sham mice ([PSV-EDV]/PSV; Mean±SEM;0.61±0.01 vs. 0.45±0.01, t test, p=0.0007). In addition, sFlt-1 reduced endothelial-dependent relaxation to acetylcholine (concentration-response, 1nM-10µM, 2-way ANOVA w/RM, p&lt;0.0001), indicating endothelial dysfunction. sFlt-1 also reduced smooth muscle relaxation responses to sodium nitroprusside (p&lt;0.05). To test whether sFlt-1 induces leptin production, we bred BALB/c mice as described above. At GD12, mice were treated with either sFlt-1 (sc.10 µg) or saline (n=6/group). After 24 h, mice were euthanized, and plasma and subcutaneous adipose tissue were collected. Our data showed an increase in plasma leptin in sFlt-1 group (ng/mL;5.0 ±0.2 vs. 2.9±0.1, t test, p&lt;0.0001) and an upregulation in placental leptin gene expression (normalized to 18S; fold change to control; 7.8±1.8 vs. 1.1±0.3, t test, p&lt;0.05). In conclusion, our data indicates that sFlt-1 induces vascular endothelial dysfunction and increases leptin plasma levels and gene expression in preeclampsia.

A case study of multiple placental cysts complicated by severe fetal growth restriction

A case study of multiple placental cysts complicated by severe fetal growth restriction

Effect and Predictive Value of Blood HbA1c, FBG, 2hPBG, and FINS on the Pregnancy Outcome in Patients with Gestational Diabetes Mellitus.

This study aimed to investigate the effects of hemoglobin A1c (HbA1c), fasting blood glucose (FBG), 2-hours postprandial blood glucose (2hPBG), and fasting insulin (FINS) levels on pregnancy outcomes and their predictive value in patients with gestational diabetes mellitus (GDM). A total of 109 pregnant women with GDM (GDM group) were included and assayed for serum FBG, 2hPBG, HbA1c, and FINS levels. The incidence of adverse pregnancy outcomes was recorded. GDM patients were divided into the poor pregnancy outcome group and the favorable pregnancy outcome group and analyzed for HbA1c, FBG, 2hPBG, and FINS. The predictive value of serum index combined detection on GDM pregnancy outcome was assessed, and the effect of serum indices on pregnancy outcome was evaluated in GDM patients with logistic regression. In the GDM group, there were 8 cases of premature membranes breaking (7.34%), 6 cases of premature delivery (5.50%), 3 cases of hyperamniotic fluid (2.75%), 2 cases of neonatal asphyxia (1.83%), 5 cases of fetal growth restriction (4.59%), and 3 cases of low-birth-weight infants (2.75%). The total incidence of adverse preg-nancy outcomes was 24.77% (27/109). HbA1c, FBG, 2hPBG, and FINS in the poor pregnancy outcome group were higher than those in the favorable pregnancy outcome group. The AUC value of blood biochemical indicators combined detection in predicting pregnancy outcome in GDM patients was higher than of HbA1c, FBG, 2hPBG, and FINS alone detection. HbA1c ≥ 6.94%, FBG ≥ 7.18 mmol/L, 2hPBG ≥ 9.36 mmol/L, and FINS ≥ 13.07 U/L were the risk factors affecting pregnancy outcomes in GDM patients. The changes of HbA1c, FBG, 2hPBG, and FINS levels in GDM patients are associated with adverse pregnancy outcomes, and the combined detection of serum indicators has predictive value for pregnancy outcomes in GDM patients.

Particulate matter-induced fetal growth restriction is associated with impaired placental bioenergetics

Particulate matter-induced fetal growth restriction is associated with impaired placental bioenergetics

Utility of placental biomarkers and fetoplacental Dopplers in predicting likely placental pathology in early and late fetal growth restriction – A prospective study

IntroductionThe aim of this study was to evaluate the association between placental abnormalities, placental biomarkers, and fetoplacental Dopplers in a cohort of pregnancies complicated by fetal growth restriction (FGR). We also ascertained the risk of perinatal mortality, severe neurological morbidity, and severe non-neurological morbidity by type of placental abnormality. MethodsThis was a prospective cohort study. Multivariable logistic regression was used to evaluate the effect of early vs. late FGR, placental biomarkers and fetoplacental Dopplers on Maternal Vascular Malperfusion (MVM) which was the commonest placental abnormality identified. ResultsThere were 161 (53.5 %) early FGR and 140 (46.5 %) late FGR cases. MVM abnormalities were present in 154 (51.2 %), VUE in 45 (14.6 %), FVM in 16 (5.3 %), DVM in 14 (4.7 %) and CHI in 4 (1.3 %) cases. The odds of MVM were higher in early compared to late FGR cohort (OR 1.89, 95%CI 1.14, 3.14, p = 0.01). Low maternal PlGF levels <100 ng/L (OR 2.34, 95%CI 1.27,4.31, p = 0.01), high sFlt-1 level (OR 2.13, 95%CI 1.35, 3.36, p = 0.001) or elevated sFlt-1/PlGF ratio (OR 3.48, 95%CI 1.36, 8.91, p = 0.01) were all associated with MVM. Increased UA PI > 95th centile (OR 2.91, 95%CI 1.71, 4.95, p=<0.001) and mean UtA PI z-score (OR 1.74, 95%CI 1.15, 2.64, p = 0.01) were associated with higher odds of MVM. Rates of severe non-neurological morbidity were highest in the MVM, FVM, and CHI cohorts (44.8 %, 50 %, and 50 % respectively). ConclusionMVM was the commonest placental abnormality in FGR, particularly in early-onset disease. Low maternal PlGF levels, high sFlt-1 levels, elevated sFlt-1/PlGF ratio, and abnormal fetoplacental Dopplers were also significantly associated with MVM. MVM, FVM, and CHI abnormalities were associated with lower median birthweight, higher rates of preterm birth, operative birth for non-reassuring fetal status, and severe neonatal non-neurological morbidity.

Impact of a Stage-Based Classification on the Incidence of Fetal Growth Restriction, Preterm Birth Rates, and Birthweight in a Rural Community of Central India

Introduction: The objective of this study was to determine the impact of the stage-based classification of fetal growth restriction (FGR) on the magnitude of FGR, preterm births (PTBs), and birthweight (BW) in a rural population of Madhya Pradesh in Central India. Methods: The program covered 168 public sector centers for pregnant women and infants that provided services to nearly 220,000 people. The third-trimester assessments included fetal biometry, growth and environment assessments, and Doppler assessments. Fetal growth was staged using the Barcelona protocol as stages 1–4 FGR, small for gestational age, and no FGR. The data from the last ultrasound assessment before childbirth were considered. Regular training programs covering preconception care, antenatal and postnatal care were organized in the local language for the public sector community health workers of the program district. Childbirth outcomes were collected from the obstetric service of the local public sector hospital. Results: The analysis included 1,229 pregnancies from 2019 to 2023. The overall magnitude of FGR using estimated fetal weight <10th centile was 19.61% and reduced to 13.34% with the stage-based classification. The magnitude of FGR using the stage-based classification reduced from 27.59% in 2019 to 8.95% in 2023. The PTB in the stage-based FGR subgroup declined from 35.0% in 2019 to 3.45% in 2023 and 96.55% of the stage 1 FGR babies in 2023 were delivered at term. The overall mean BW in the program area improved from 2,772.41 (357.11) g in 2019 to 2,819.68 (377.31) g in 2023. The perinatal mortality rate (8.95 per 1,000 pregnancies) in the program area for 2019–2023 was much lower than the 31.9 per 1,000 pregnancies reported for Madhya Pradesh. Conclusion: The change to a stage-based classification of FGR integrated with low-dose aspirin and fetal Doppler studies reduced the incidence of FGR and PTB and perinatal mortality and increased BW in this rural community.