1.1.        Background

Fetal development disorders such as intrauterine growth retardation (IUGR) are identified by the weight of the fetus that is below 10 percent of the appropriate gestational age range. In the third trimester of clinically suspected IUGR pregnancies, we sought to assess the relevance of Doppler velocimetry in the clinical treatment of such pregnancies as well as the prognostic value of Middle cerebral artery (MCA) Doppler indices in unfavorable perinatal outcomes. Because IUGR patients have lower PI and RI values than Non-IUGR patients, the purpose of this study is to ascertain whether there is a difference between the Doppler indices of IUGR and Non-IUGR patients.

1.2.        Introduction

A fetus classified as non-intrauterine growth restricted (Non-IUGR) is one whose birth weight is significantly normal; on the other hand, a fetus classified as intrauterine growth restricted (IUGR) is one whose birth weight is significantly lower than the normal weight (less than the 10th percentile) for that gestational age (Sharma et al., 2016). Many diseases that cause fetal cell size reduction, when they occur early and in sufficient numbers, can lead to IUGR (Anjum & Lakshmi, 2019). Fetal weight assessed by sonography that is below ten percent for gestational age is known as intrauterine growth restriction (Javaid et al., 2010). One significant and often overlooked factor contributing to perinatal morbidity and death is intrauterine growth restriction (IUGR). Compared to wealthy countries, the rate of IUGR in underdeveloped countries is six times greater. Every year, IUGR affects 14–20 million newborns and between 10-15% of expectant mothers in underdeveloped nations. The highest prevalence is reported in South-Central Asia (33%) and India (21%)(Yadav et al., 2020). Although IUGR is a prenatal diagnosis, some of these fetuses may only be discovered postnatally, particularly if screening was not conducted throughout pregnancy. The placenta provides the sole nourishment that the fetus has access to. Developmental issues arise from the placenta's limited capacity to supply the fetus with sufficient nutrients during intrauterine growth restriction (IUGR) (Bano S et al., 2010). The mother has a multitude of influences on the fetus's growth. Adequate blood flow to both the mother and the fetus is necessary for appropriate placental function and, therefore, fetal development. Any disruption to the placental circulation causes placental insufficiency, which in turn encourages compensatory alterations in the circulation of the fetus.

Growth-restricted fetuses are a problem that obstetricians must detect since it is typically linked with considerable morbidity and/or death (Suhag A & Berghella V, 2013). One of the most prevalent pregnancy-related issues that is linked to iatrogenic prematurity is IUGR. Irregular placentation is the most common cause of IUGR, and the condition's outcomes are often linked to reduced placental blood flow (ACOG Practice Bulletin No. 134: Fetal Growth Restriction, 2013). IUGR can be caused by a wide range of factors, including: aberrant uteroplacental circulation and abnormal fetoplacental circulation are examples of placental insufficiency. Conditions that affect mothers include drug and alcohol abuse, smoking, fetal alcohol syndrome, diabetes, hunger, and vascular diseases (Weerakkody Y et al., 2010). Early detection of placental insufficiency is crucial for minimizing its risks (Naleini F et al., 2017).

Identifying and treating IUGR early on is one of the greatest accomplishments in modern obstetrics. Fetal growth evaluation at every prenatal visit is essential to prevent perinatal mortality and morbidity if the growth-restricted fetus is detected and appropriate care is implemented.  The purpose of this study is to enhance our institute's diagnostic, preventative, and curative capabilities for the best possible outcomes for newborn health.

Prior to this, the only physical tests used to diagnose IUGR in a timely manner were fundal height, belly circumference, and maternal weight charts. Serial biometry later gained importance once sonography became available. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight, amniotic fluid index (AFI), and placental alterations are all measured with routine ultrasound imaging. Patients are classified as cases, or those with IUGR, and controls, or non-IUGR, based on ultrasound results. Doppler studies are conducted after IUGR instances. Neonatal birth weight, ponderal index, and prenatal outcome are recorded for every patient who is monitored until delivery (Yadav SS et al., 2020).

A noninvasive diagnostic tool called Doppler ultrasonography can be utilized to measure blood flow via the blood vessels by measuring the high-frequency sound waves (ultrasound) reflected off of circulating red blood cells.

When screening high-risk pregnancies, Doppler ultrasonography is a crucial component of clinical practice. It detects placental circulatory failure and provides immediate information on fetoplacental circulation. Pregnancy is one of the most important times to use color Doppler assessment, which is one of the most commonly accepted functional ways to assess fetal health. From the beginning of pregnancy until term, flow velocity waveforms offer crucial information. A special method for the non-invasive assessment of the utero-placental and feto-placental rotation is provided by Doppler sonography (Anjum & Lakshmi., 2019).

Doppler ultrasonography has the benefit of being a quick, repeatable, and everyday procedure. Throughout the last trimester of pregnancy, fetal well-being is screened using a middle cerebral artery (MCA) Doppler. Because it is easy to identify and reproducible, it is the most often photographed intracranial vessel. MCA Doppler may detect an upsurge in diastolic blood velocity to the brain in the IUGR-affected fetus (Baschat et al., 2007).

Changes in the direction and magnitude of cerebral blood flow can also be used to predict fetal outcomes by measuring the middle cerebral artery (MCA). It has been established that the fetus's cerebral artery has significant resistance during the prenatal stage. But in dangerous situations like hypoxemia and placental insufficiency, this parameter might shift because chemoreceptors are activated and vasodilator or vasoconstrictor substances are altered (Aditya I et al., 2016). Doppler imaging is considered for monitoring high-risk pregnancies or fetuses identified with IUGR on grayscale results after biometric data have been evaluated. The apparent shift in frequency of a wave, be it sound or light, as its source becomes closer or farther away from the observer is known as the Doppler Effect, which was first reported by Christian Doppler in 1842.

Doppler ultrasonography has made it possible to track the utero-placental, and feto-placental rotations of high threat of pregnancies. The non-invasive Doppler method is also utilized to evaluate the reaction of fetal circulation to hypoxia. We can see different spectrum waveforms or flow velocity waveforms of the vessels that support the uteroplacental and fetoplacental circulations thanks to Doppler methods. It is possible to evaluate a number of metrics, including systolic to diastolic (S/D) ratios, resistivity index (RI), and pulsatility index (PI) (Kuber et al., 2016).

This study aims to assess differences in MCA Doppler parameters, comprising pulsatility index (PI), resistance index (RI), and S/D ratio, between these groups. By analyzing these indices, the research seeks to identify potential alterations in fetal cerebral hemodynamics associated with IUGR, which may serve as early indicators of fetal well-being. This study intends to contribute to the understanding of fetal hemodynamic adaptations in the context of IUGR and may have implications for the antenatal surveillance and management of pregnancies complicated by growth restriction.

An analytical comparative cross-sectional study was conducted at the Radiology Department of AL-Nusrat Clinic in Sadiqabad, Pakistan, over a period of three months following formal approval of the research synopsis from the institutional review committee. A total sample size of N=100 fetuses was enrolled using a convenience sampling technique, divided equally into two groups comprising 50 fetuses with intrauterine growth restriction (IUGR) and 50 non-IUGR control fetuses. Pregnant women presenting for routine or indicated prenatal ultrasound examinations between 28 and 41 weeks of gestation were evaluated and selected based on strict eligibility criteria. Inclusion criteria include singleton pregnancies, third-trimester gestations, gestational ages ranging between 28 and 40 weeks, and clinically presumed intrauterine development impediment characterized by an estimated fetal weight below the 10th percentile. Exclusion criteria include multiple gestations, congenital fetal deformities, prenatally recognized chromosome abnormalities, early and preterm rupture of membranes, unclear gestational ages, concurrent diabetes mellitus, chronic hypertension, and anatomical abnormalities. All participants provided signed, fully informed consent after being briefed on potential study risks, benefits, and their absolute right to voluntarily withdraw from the study at any point without penalty. Complete participant confidentiality and data anonymity were ensured throughout all phases of the research, and measures were taken to protect participant privacy in any resulting publications. Ultrasonographic evaluations were performed by experienced radiologists utilizing a GE LOGIQ E9 (Rev 5) machine equipped with a curved-array transducer (2.5–3.5 MHz). Prior to Doppler assessment, each participant underwent standard gray-scale ultrasound evaluation, including targeted fetal anatomy scanning to exclude congenital structural anomalies and fetal biometry comprising biparietal diameter (BPD), head circumference (HC), and femur length (FL) measurements. Estimated fetal weight (EFW) was calculated from these biometric measurements. Pulsed-wave color Doppler velocimetry of the middle cerebral artery (MCA) was subsequently performed using a color Doppler ultrasound system. The angle between the direction of blood flow and the ultrasonic beam was maintained at less than 35 degrees, identifying the MCA via the cord's free-floating loop to collect flow velocity waveforms regardless of end-diastolic velocity presence, from which the pulsatility index (PI), resistance index (RI), and systolic-to-diastolic (S/D) ratio were meticulously calculated. The collected data were entered and analyzed using IBM SPSS Statistics software. Quantitative continuous variables were summarized as means and standard deviations, whereas qualitative parameters were presented as absolute frequencies and percentages. The Shapiro–Wilk test was applied to assess data normality. Comparative analysis of MCA Doppler indices, EFW, and demographic variables between the IUGR and non-IUGR groups was executed using independent-samples t-tests. Levene's test for equality of variances was conducted to assess variance homogeneity, and a two-sided p-value of less than or equal to 0.05 was considered statistically significant.

A convenience sample of 100 pregnant individuals in their third trimester (28–40 weeks' gestation) with single, clinically suspected intrauterine growth restriction (IUGR) cases was included. Exclusion criteria were multiple gestations, unclear gestational age, congenital anomalies, premature rupture of membranes, pre-existing diabetes, anatomical abnormalities, and chronic hypertension. Using a GE LOGIQ E9 (Rev 5) ultrasonography system with a curved probe, Doppler indices, specifically Pulsatility Index (PI) and Resistive Index (RI), were evaluated to compare differences between IUGR and non-IUGR pregnancies.

The descriptive statistics for the age of the 100 participants show a mean age of 29.68 years with a standard deviation of 4.07 years. The ages of the participants spanned from a minimum of 20 years to a maximum of 39 years, indicating a well-distributed maternal age range within the study cohort (Table 1).

Regarding gestational age distribution among the 100 participants: 4% had a gestational age of 27 weeks, 8% had 28 weeks, 9% had 29 weeks, 15% had 30 weeks, 6% had 31 weeks, 16% had 32 weeks, 2% had 33 weeks, 5% had 34 weeks, 20% had 35 weeks, 6% had 36 weeks, 3% had 37 weeks, and 6% had 38 weeks (Table 2).

Group statistics for Middle Cerebral Artery (MCA) Doppler indices in IUGR and non-IUGR groups showed that the mean MCA S/D ratio of 50 IUGR patients was 2.95 (), and for non-IUGR patients it was 5.99 (). The mean MCA RI of 50 IUGR patients was 0.66 (), and for non-IUGR patients it was 0.80 (). The mean MCA PI of 50 IUGR patients was 0.83 (), and for non-IUGR patients it was 1.23 () (Table 3).

Independent samples t-tests assessing the equality of means for various Doppler indices between groups with and without intrauterine growth restriction (IUGR) indicated that Levene's test showed significant differences in variances for all indices with a p-value of 0.000. When assuming equal variances, the t-tests revealed statistically significant differences in means between IUGR groups for all Doppler indices, implying significant hemodynamic variations of MCA Doppler indices between IUGR and non-IUGR cases (Table 4).

Group statistics of estimated fetal weight (EFW) for the two groups categorized by IUGR showed that the mean EFW of 50 IUGR patients was 1582.06 g (), while the mean EFW of 50 non-IUGR patients was 1999.34 g () (Table 5).

Levene's test for equality of variances showed a significant result (, ), indicating unequal variances between the groups. The t-test assuming equal variances showed a statistically significant change in the mean EFW between the IUGR and non-IUGR groups (). The mean difference was -417.27 grams, with a standard error of 64.38, and the 95% confidence interval of the difference ranged from -544.017 to -290.531. When equal variances were not assumed, the results remained significant (, , ), indicating a robust difference in EFW between the groups. These findings suggest that there is a significant disparity in estimated fetal weight between individuals with and without intrauterine growth restriction (Table 6).

Table 1. Descriptive statistics for age

Table 2. Frequency Distribution of G.A

Table 3. Group statistics for MCA Doppler indices in IUGR and non-IUGR.

Table 5. Group statistics of estimated fetal weight (EFW) for two groups categorized by IUGR.

Table 6. Independent samples t-test

Fig. 1.1 shows the difference between NON-IUGR and IUGR fetuses

(Karlsen H et al., 2016)

Figure1.2 shows the causes of IUGR fetuses. (Aye et al., 2013)

Figure1.3 Normal aspect of middle cerebral artery circulation, with low diastole

(Muresan et al., 2016)

Figure1.4 Cerebral vasodilatation in the middle cerebral artery with increased diastole

(Muresan et al., 2016)

Figure 1.5 Showing reduced Doppler indices reflecting the “brain-sparing effect” in the MCA

(Kuber, et al., 2016).

IMAGE 1: Ultrasound image shows low Doppler indices of MCA in

IUGR fetus in the third trimester

IMAGE 2: Ultrasound image shows normal Doppler indices of

MCA in a non-IUGR fetus in the third trimester.

IMAGE 3: Ultrasound image shows altered Doppler indices of

MCA in an IUGR fetus in the third trimester

IMAGE 4: Ultrasound image shows high diastolic flow of MCA in

IUGR fetus in the third trimester

Intrauterine growth restriction (IUGR)—defined as estimated fetal weight (EFW) <10th percentile for gestational age—affects 24% of pregnancies globally (over 30 million infants annually), causing high rates of neonatal morbidity and mortality (Sharma et al., 2021; Yakout et al., 2021). Its main underlying cause is chronic uteroplacental insufficiency, which impairs fetal oxygenation and nutrient transfer (Kuber et al., 2016). In response to hypoxia, the fetus undergoes a protective "brain-sparing" adaptation, redistributing cardiac output toward the brain via cerebral arterial vasodilation (Desai et al., 2017). This hemodynamic shift causes a distinct drop in Middle Cerebral Artery (MCA) Doppler parameters, including the Resistance Index (RI), Pulsatility Index (PI), and Systolic-to-Diastolic (S/D) ratio (Desai et al., 2017; Nazir et al., 2021). Numerous studies validate MCA Doppler ultrasonography as a rapid, non-invasive method for detecting fetal hypoxia (Anjum & Lakshmi, 2019; Ismail et al., 2022). Ismail et al. (2022) and Desai et al. (2017) demonstrated significantly lower MCA RI and PI values in third-trimester IUGR fetuses compared to normal controls, directly reflecting hypoxia-induced cerebral vasodilation. Furthermore, abnormal MCA indices correlate strongly with poor perinatal outcomes, including low Apgar scores, oligohydramnios, and increased NICU admissions (Anjum & Lakshmi, 2019; Yakout et al., 2021). While multi-vessel assessment—such as the Cerebroplacental Ratio (CPR)—offers strong predictive value (Sharma et al., 2021), tracking standalone MCA Doppler indices remains a critical, accessible tool for identifying compromised fetuses and timing antenatal interventions in regional clinical settings (Khadija et al., 2020; Refaat et al., 2021). This study compared MCA Doppler parameters between third-trimester IUGR and non-IUGR fetuses at AL-Nusrat Clinic in Sadiqabad, Pakistan. The findings demonstrated statistically significant reductions in MCA S/D ratio (2.95±0.52 vs. 5.99±1.12), RI (0.66±0.08 vs. 0.80±0.05), and PI (0.83±0.20 vs. 1.23±0.37) in IUGR cases compared to non-IUGR controls (p<0.001). These reduced indices, alongside a significantly lower mean estimated fetal weight (1582.06g vs. 1999.34g, p<0.001), confirm active compensatory cerebral vasodilation (the "brain-sparing effect") in response to placental insufficiency within our cohort. Our results align closely with existing literature. The mean maternal age (29.68±4.07 years) and gestational age profile parallel demographic data reported by Nazir et al. (2021) and Sharma et al. (2021). Furthermore, the pronounced drop in MCA PI, RI, and S/D ratios in growth-restricted fetuses matches findings by Ismail et al. (2022) in Faisalabad and Desai et al. (2017), who established that fetal hypoxia drives down downstream cerebral impedance. As highlighted by Kuber et al. (2016) and Yakout et al. (2021), while primary placental damage raises umbilical resistance, secondary MCA vasodilation acts as a vital neural protective mechanism, serving as a reliable clinical indicator of fetal risk. Key study limitations include a single-center design, convenience sampling, a small sample size (N=100), and the lack of post-natal outcome tracking (e.g., Apgar scores or NICU admissions). Future multi-center prospective studies with larger cohorts, multi-vessel Doppler protocols (incorporating UA and CPR), and longitudinal neonatal follow-up are recommended to establish localized diagnostic cutoffs and optimize delivery timing in Pakistan.

In conclusion, this study provides valuable clinical insights into fetal hemodynamic adaptations by comparing middle cerebral artery (MCA) Doppler indices between third-trimester intrauterine growth restriction (IUGR) and non-IUGR singleton pregnancies. Based on the evaluation of 100 participants, the findings demonstrate statistically significant differences (p<0.001) in MCA Doppler parameters, with the mean Pulsatility Index (PI), Resistive Index (RI), and Systolic/Diastolic (S/D) ratio being notably lower in IUGR cases compared to normal controls. This observed reduction in MCA resistance indices confirms the physiological manifestation of the cerebral "brain-sparing" reflex, where chronic uteroplacental insufficiency and hypoxia trigger cerebral vasodilation to protect vital organ perfusion. Additionally, a significant difference in estimated fetal weight (EFW) was established between the groups (p<0.001), reinforcing the physical impact of third-trimester growth restriction. Ultimately, routine spectral Doppler evaluation of the MCA serves as an accessible, non-invasive, and reliable diagnostic tool, enabling healthcare practitioners to enhance fetal surveillance, optimize the timing of delivery, and improve perinatal outcomes in high-risk populations.