Fetal growth restriction (FGR), defined as failure of a fetus to achieve its genetically predetermined growth potential, affects approximately 5-10% of pregnancies worldwide and represents a major cause of perinatal morbidity and mortality [1]. FGR is linked with increased risks of stillbirth, neonatal complications, and long-term adverse health outcomes, such as cardiovascular disease, metabolic syndrome, and neurodevelopmental impairment in later life [2, 3]. FGR is multifactorial, involving maternal, placental, and fetal factors, with uteroplacental insufficiency being the most common factor in developed nations [4]. Pregnancy induces intense changes in maternal lipid metabolism to establish the increased energy demands of the growing fetus and prepare for lactation [5]. During normal pregnancy, maternal lipid levels progressively increase, with triglycerides rising by 2-3 fold and cholesterol increasing by approximately 25-50% by the third trimester [6]. These physiological adaptations are mediated by pregnancy hormones, including estrogen and progesterone, which influence hepatic lipid synthesis and lipoprotein metabolism [7]. The maternal-fetal transfer of lipids is vital for fetal development, particularly for brain growth, cellular membrane synthesis, and steroid hormone production [8]. Alterations in maternal lipid metabolism have been implicated in various pregnancy complications, such as preterm birth, preeclampsia, and gestational diabetes mellitus (GDM) [9, 10]. Recent evidence suggests that abnormal maternal lipid profiles may also play a role in abnormal fetal growth patterns. Studies have reported associations between maternal dyslipidemia and macrosomia in cases of maternal obesity and diabetes [11]. However, the relationship between maternal lipid parameters and FGR has received less attention and remains controversial. Some investigators have reported lower maternal lipid levels in pregnancies complicated by FGR in comparison with the normal pregnancies [12, 13], while others found elevated lipid levels or no significant differences [14]. Koukkou et al. documented that women carrying growth-restricted fetuses had lower serum triglyceride concentrations in the second and third trimesters [12]. Similarly, Misra et al. reported reduced maternal cholesterol and triglyceride levels in FGR pregnancies [15]. These findings suggest that inadequate maternal lipid supply or impaired placental lipid transfer may contribute to fetal undergrowth. The potential link between maternal lipids and fetal growth is multifaceted. Lipids are important substrates for fetal energy metabolism and structural development [16]. Maternal triglycerides cannot cross the placenta directly but are hydrolyzed by placental lipases, releasing fatty acids that are then transferred to the fetus [17]. Cholesterol is necessary for cell membrane synthesis and functions as a precursor for steroid hormones and biliary acids [18]. Disruption in these processes, whether due to maternal lipid deficiency or placental dysfunction, could potentially compromise fetal growth. Despite these observations, significant knowledge gaps remain. Most previous studies have been constrained by small sample sizes, heterogeneous populations, and variable definitions of FGR. The independent contribution of specific lipid parameters to FGR risk, after controlling for confounding factors, requires further elucidation. Additionally, the clinical utility of maternal lipid assessment as a potential biomarker for FGR identification warrants investigation. Aim of the study: This prospective case-control study aimed to comprehensively determine the association between maternal lipid profile parameters and FGR, and to determine whether maternal dyslipidemia independently predicts FGR after adjusting for traditional risk factors.

This prospective case-control study was conducted in three departments (Obstetrics & Gynecology, General Medicine and General Surgery) of Dr Moopen’s Medical College, Wayanad, Kerala. A total of 240 pregnant women were recruited at 28-34 weeks of gestation, comprising 120 cases with sonographically diagnosed FGR and 120 controls with appropriate-for-gestational-age (AGA) fetuses. Sample size was calculated using a two-sample t-test formula with 90% power and 5% significance level, assuming a mean difference of 30 mg/dL in triglyceride levels with a standard deviation of 50 mg/dL, yielding a minimum required sample of 112 per group. The sample was inflated to 120 per group to account for potential dropouts. Inclusion and Exclusion Criteria Inclusion criteria for cases included: (1) singleton pregnancy, (2) gestational age 28-34 weeks confirmed by first-trimester ultrasound, (3) estimated fetal weight (EFW) below the 10th percentile for gestational age based on the Hadlock formula, (4) absence of structural or chromosomal fetal abnormalities, and (5) maternal age 18-42 years. Controls were matched for gestational age and had EFW between the 10th and 90th percentiles. Exclusion criteria included: (1) multiple pregnancies, (2) pre-existing diabetes mellitus or GDM, (3) chronic hypertension or preeclampsia, (4) maternal chronic diseases affecting lipid metabolism (thyroid disorders, renal disease, liver disease), (5) current use of lipid-lowering medications or corticosteroids, (6) known fetal genetic or structural abnormalities, (7) confirmed fetal infections, and (8) maternal smoking or substance abuse. Clinical Assessment and Data Collection Comprehensive maternal demographic and clinical information were gathered using standardized questionnaires, including maternal age, parity, pre-pregnancy body mass index (BMI), medical history, obstetric history, and socioeconomic status. Detailed obstetric history included previous pregnancies, complications, and pregnancy outcomes. Anthropometric measurements were performed according to standardized protocols. Pre-pregnancy BMI was determined from self-reported pre-pregnancy weight and measured height. Gestational weight gain was assessed at the time of enrollment. Blood pressure measurements were obtained following standard guidelines. Ultrasound Assessment All ultrasound examinations were performed by certified maternal-fetal medicine specialists using high-resolution ultrasound machines (GE Voluson E10, GE Healthcare). Fetal biometry included biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). EFW was determined employing the Hadlock formula. Amniotic fluid index (AFI) was calculated using the four-quadrant technique. Umbilical artery Doppler velocimetry was performed to assess placental resistance, with pulsatility index (PI) recorded. Biochemical Analysis After 10-12 hours overnight fasting, venous blood samples (10 mL) were collected between 28-34 weeks of gestation. Samples were centrifuged at 3000 rpm for 10 minutes, and serum was separated and stored at -80°C until analysis. Fasting lipid profile was recorded using enzymatic colorimetric methods on an automated biochemistry analyzer (Cobas 8000, Roche Diagnostics). The following parameters were assessed: • Total cholesterol (TC) • Triglycerides (TG) • High-density lipoprotein cholesterol (HDL-C) • Low-density lipoprotein cholesterol (LDL-C) calculated using Friedewald equation: LDL-C = TC - HDL-C - (TG/5) • Very low-density lipoprotein cholesterol (VLDL-C) = TG/5 Atherogenic indices were calculated: • TC/HDL-C ratio • TG/HDL-C ratio • LDL-C/HDL-C ratio • Atherogenic index of plasma (AIP) = log(TG/HDL-C) Additional biochemical investigations such as fasting glucose, hemoglobin, serum albumin, and liver enzymes, were also measured. Pregnancy Outcome Monitoring All participants were followed until delivery. Neonatal outcomes recorded included birth weight, gestational age at delivery, Apgar scores, need for neonatal intensive care unit (NICU) admission, and neonatal complications. Birth weight percentiles were calculated using standardized growth charts. Statistical Analysis Statistical analysis was performed using SPSS version 27.0 (IBM Corp., Armonk, NY). Normality of continuous variables was tested using the Shapiro-Wilk test and Q-Q plots. Continuous variables were expressed as mean ± standard deviation (SD) for normally distributed data or median (interquartile range) for non-normal distribution. Categorical variables were presented as frequencies and percentages. An independent t-test or Mann-Whitney U test was used for cotrasting continuous variables between groups as appropriate. Chi-square test or Fisher's exact test was employed for categorical variables. Pearson or Spearman correlation coefficients were applied to determine relationships between maternal lipid parameters and fetal/neonatal growth parameters. Multivariate logistic regression analysis was used to identify independent predictors of FGR, adjusting for potential confounders including maternal age, parity, pre-pregnancy BMI, gestational weight gain (GWG), and hemoglobin levels. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. A two-tailed p-value <0.05 was deemed statistically significant.

Baseline Maternal Characteristics Table 1 presents the baseline demographic and clinical characteristics. There were insignificant differences between FGR and control groups in terms of maternal age (28.6 ± 5.2 vs. 29.1 ± 4.8 years, p=0.428), parity distribution (p=0.632), or pre-pregnancy BMI (23.4 ± 3.6 vs. 24.1 ± 3.4 kg/m², p=0.112). However, GWG was significantly lower in the FGR group (9.2 ± 3.4 vs. 11.8 ± 3.6 kg, p<0.001). Women in the FGR group had lower mean hemoglobin scores (10.8 ± 1.2 vs. 11.4 ± 1.1 g/dL, p<0.001) and higher anemia prevalence (45.8% vs. 26.7%, p=0.002). Table 1. Baseline Maternal Demographic and Clinical Characteristics Characteristics FGR (n=120) Controls (n=120) p-value Maternal age (years) 28.6 ± 5.2 29.1 ± 4.8 0.428 Gestational age at assessment (weeks) 31.2 ± 1.8 31.4 ± 1.6 0.356 Pre-pregnancy BMI (kg/m²) 23.4 ± 3.6 24.1 ± 3.4 0.112 Gestational weight gain (kg) 9.2 ± 3.4 11.8 ± 3.6 <0.001 Nulliparous, n (%) 54 (45.0) 50 (41.7) 0.632 Multiparous, n (%) 66 (55.0) 70 (58.3) Hemoglobin (g/dL) 10.8 ± 1.2 11.4 ± 1.1 <0.001 Anemia (Hb <11 g/dL), n (%) 55 (45.8) 32 (26.7) 0.002 Systolic BP (mmHg) 116.4 ± 12.6 114.2 ± 10.8 0.146 Diastolic BP (mmHg) 74.2 ± 8.4 72.6 ± 7.8 0.128 Previous FGR, n (%) 18 (15.0) 3 (2.5) <0.001 History of miscarriage, n (%) 28 (23.3) 22 (18.3) 0.342 Maternal Lipid Profile and Fetal Parameters Table 2 demonstrates significant differences in maternal lipid profile parameters between groups. Women in the FGR group had significantly lower mean serum triglycerides (198.4 ± 42.6 vs. 246.8 ± 51.2 mg/dL, p<0.001), TC (224.6 ± 38.4 vs. 248.3 ± 42.1 mg/dL, p<0.001), and HDL-C (56.2 ± 12.4 vs. 62.8 ± 14.2 mg/dL, p=0.001) as contrasted with the control group. LDL-C levels were also lower in the FGR group (128.6 ± 32.4 vs. 136.2 ± 34.8 mg/dL, p=0.042). VLDL-C levels were significantly reduced in FGR cases (39.7 ± 8.5 vs. 49.4 ± 10.2 mg/dL, p<0.001). Among atherogenic indices, the TG/HDL-C ratio was significantly lower in the FGR group (3.72 ± 1.18 vs. 4.15 ± 1.32, p=0.008), while TC/HDL-C and LDL-C/HDL-C ratios indicated insignificant differences. Hypotriglyceridemia (TG <200 mg/dL) was observed among 60.8% of FGR cases in contrast to 32.5% of controls (p<0.001). Fetal ultrasound parameters demonstrated expected differences. Mean EFW was 1458 ± 286 g in the FGR group versus 2104 ± 324 g in controls (p<0.001). Abnormal umbilical artery Doppler (PI >95th percentile) was present in 42.5% of FGR cases. Oligohydramnios (AFI <5 cm) occurred in 28.3% of FGR cases compared to 2.5% of controls. Table 2. Comparison of Maternal Lipid Profile and Fetal Parameters Parameter FGR (n=120) Controls (n=120) p-value Lipid Profile (mg/dL) TC 224.6 ± 38.4 248.3 ± 42.1 <0.001 Triglycerides 198.4 ± 42.6 246.8 ± 51.2 <0.001 HDL-cholesterol 56.2 ± 12.4 62.8 ± 14.2 0.001 LDL-cholesterol 128.6 ± 32.4 136.2 ± 34.8 0.042 VLDL-cholesterol 39.7 ± 8.5 49.4 ± 10.2 <0.001 Atherogenic Indices TC/HDL-C ratio 4.18 ± 1.12 4.08 ± 1.04 0.462 TG/HDL-C ratio 3.72 ± 1.18 4.15 ± 1.32 0.008 LDL-C/HDL-C ratio 2.38 ± 0.82 2.25 ± 0.76 0.184 Atherogenic index of plasma 0.54 ± 0.18 0.59 ± 0.16 0.018 Lipid Categories, n (%) Hypotriglyceridemia (TG <200 mg/dL) 73 (60.8) 39 (32.5) <0.001 Hypocholesterolemia (TC <220 mg/dL) 52 (43.3) 28 (23.3) 0.001 Low HDL-C (<50 mg/dL) 36 (30.0) 24 (20.0) 0.074 Fetal Parameters Estimated fetal weight (g) 1458 ± 286 2104 ± 324 <0.001 EFW percentile 6.4 ± 2.8 48.2 ± 22.6 <0.001 Abnormal umbilical artery Doppler, n (%) 51 (42.5) 4 (3.3) <0.001 Oligohydramnios (AFI <5 cm), n (%) 34 (28.3) 3 (2.5) <0.001 Correlation Analysis and Pregnancy Outcomes Table 3 presents correlation analysis between maternal lipid parameters and neonatal outcomes, as well as multivariate regression analysis for FGR predictors. Birth weight revealed a significant positive correlation with maternal TG (r = 0.418, p<0.001), TC (r = 0.321, p<0.001), and VLDL-C (r = 0.396, p<0.001). Moderate positive correlation was observed between birth weight and HDL-C (r = 0.247, p<0.001). Neonatal outcomes demonstrated significant differences between groups. The average birth weight was 2164 ± 412 g in the FGR group versus 3086 ± 386 g in controls (p<0.001). Mean gestational age at delivery was lower in the FGR group (36.8 ± 2.1 vs. 38.6 ± 1.4 weeks, p<0.001). NICU admission rate was significantly higher in FGR neonates (48.3% vs. 8.3%, p<0.001). Multivariate logistic regression analysis, adjusting for maternal age, parity, pre-pregnancy BMI, GWG, hemoglobin, and previous FGR, identified maternal triglyceride levels <200 mg/dL as an independent predictor of FGR (adjusted OR = 3.24, 95% CI: 1.82-5.77, p<0.001). Total cholesterol <220 mg/dL was also independently associated with FGR (adjusted OR = 2.18, 95% CI: 1.16-4.09, p=0.015). Other independent predictors included low gestational weight gain (adjusted OR = 1.18 per kg decrease, 95% CI: 1.08-1.29, p<0.001) and previous FGR (adjusted OR = 6.42, 95% CI: 1.78-23.14, p=0.004). Table 3. Correlation Analysis and Multivariate Regression for FGR Predictors A. Correlation between Maternal Lipids and Birth Weight Lipid Parameter Correlation coefficient (r) p-value TC 0.321 <0.001 Triglycerides 0.418 <0.001 HDL-cholesterol 0.247 <0.001 LDL-cholesterol 0.198 0.002 VLDL-cholesterol 0.396 <0.001 B. Neonatal Outcomes FGR (n=120) Controls (n=120) p-value Birth weight (g) 2164 ± 412 3086 ± 386 <0.001 Gestational age at delivery (weeks) 36.8 ± 2.1 38.6 ± 1.4 <0.001 Low birth weight (<2500 g), n (%) 94 (78.3) 12 (10.0) <0.001 NICU admission, n (%) 58 (48.3) 10 (8.3) <0.001 5-min Apgar score <7, n (%) 16 (13.3) 3 (2.5) 0.002 C. Multivariate Logistic Regression for FGR Adjusted OR (95% CI) p-value Triglycerides <200 mg/dL 3.24 (1.82-5.77) <0.001 Total cholesterol <220 mg/dL 2.18 (1.16-4.09) 0.015 Low gestational weight gain (per kg decrease) 1.18 (1.08-1.29) <0.001 Maternal anemia 1.86 (1.04-3.32) 0.036 Previous FGR 6.42 (1.78-23.14) 0.004 Pre-pregnancy BMI (per kg/m²) 0.96 (0.88-1.05) 0.382

This prospective case-control study demonstrates significant associations between maternal lipid profile abnormalities and FGR. Our principal findings indicate that women carrying growth-restricted fetuses exhibit substantially lower serum TG, TC, HDL-C, and LDL-C levels compared to those with normally growing fetuses. Importantly, hypotriglyceridemia emerged as an independent risk element for FGR, with a more than three-fold increased odds after adjusting for established confounders. The observed hypotriglyceridemia in FGR pregnancies aligns with previous reports [12, 19]. Koukkou et al. reported significantly lower TG concentrations among women with FGR fetuses, particularly in the third trimester [12]. Similarly, Edison et al. demonstrated that maternal TG concentrations were positively correlated with birth weight and were lower in pregnancies resulting in small-for-gestational-age infants [19]. Our findings extend this evidence by demonstrating that this relationship persists after controlling for multiple confounding elements, suggesting an independent pathophysiological role for maternal lipid metabolism in fetal growth. The mechanisms underlying the association between low maternal TG and FGR are multifaceted. Triglycerides represent a major energy source during pregnancy, with maternal hypertriglyceridemia serving as an adaptive response to meet increased metabolic demands [20]. Lipids are essential for fetal development, particularly for neurological development and cellular membrane synthesis [21]. During the third trimester, when fetal growth accelerates dramatically, lipid requirements increase substantially. Although maternal triglycerides cannot cross the placenta intact, they are hydrolyzed by placental lipoprotein lipase and endothelial lipase, releasing free fatty acids and glycerol that are transported to the fetus [17, 22]. Inadequate maternal TG levels may reflect insufficient lipid substrate availability for fetal transfer, potentially contributing to growth restriction. Alternatively, low maternal triglycerides might indicate placental dysfunction, as impaired placental lipid metabolism could result in both reduced maternal lipid clearance and decreased fetal lipid delivery [23]. The observation that 42.5% of FGR cases in our study demonstrated abnormal umbilical artery Doppler supports the role of placental insufficiency in this context. The lower TC and LDL-C levels noted in the FGR group are also noteworthy. Cholesterol is vital for fetal development, serving as a precursor for steroid hormones and playing essential roles in cell membrane structure and signaling [24]. Although the fetus can synthesize cholesterol de novo, maternal cholesterol contribution, particularly in early pregnancy, is important for optimal development [25]. Our finding of lower maternal cholesterol in FGR cases is consistent with the findings of Misra et al. [15] and Kulkarni et al. [26], reporting similar associations. The cholesterol influences fetal growth exhibiting its role in placental steroidogenesis. The placenta produces substantial amounts of progesterone and estrogen, which require cholesterol as substrate [27]. These hormones are essential for maintaining pregnancy and supporting fetal development. Reduced maternal cholesterol availability could potentially compromise placental hormone production, indirectly affecting fetal growth. Our correlation analysis indicated significant positive associations between maternal lipid parameters and birth weight, with TG indicating the strongest correlation (r = 0.418), which are consistent with the findings of Wang et al., who demonstrated positive correlations between maternal lipids and neonatal anthropometric measurements [28]. The dose-response relationship between maternal TG and birth weight strengthens the evidence for a causal pathway. Interestingly, we observed lower TG/HDL-C ratio and atherogenic index of plasma in the FGR group. While elevated atherogenic indices are typically associated with cardiovascular risk and have been linked to preeclampsia [29], in the context of pregnancy, these indices reflect the degree of maternal metabolic adaptation. The paradoxically lower atherogenic indices in FGR may reflect overall reduced lipid mobilization and metabolism rather than a protective effect. The clinical implications of our results are crucial. Maternal lipid profile assessment during pregnancy could potentially serve as an adjunct tool for identifying pregnancies at risk for FGR, particularly when combined with other clinical and ultrasound markers. The relatively simple and widely available nature of lipid profile testing makes this approach feasible in various healthcare settings. However, before recommending routine lipid screening for FGR prediction, prospective validation studies with larger populations are necessary to establish optimal cutoff values and assess predictive performance. Whether nutritional interventions aimed at optimizing maternal lipid status could prevent or ameliorate FGR remains an important research question. Studies have explored omega-3 fatty acid supplementation in pregnancy, with mixed results regarding effects on birth weight [30]. Given our findings, targeted nutritional strategies to maintain adequate maternal lipid levels in at-risk populations warrant investigation. Several strengths of this study enhance the validity of our study outcomes. The prospective design with concurrent control group minimizes selection bias. Comprehensive assessment of multiple lipid parameters and atherogenic indices provides detailed characterization of maternal lipid metabolism. Rigorous statistical adjustment for potential confounders, including maternal anthropometric and clinical factors, strengthens the evidence for independent associations. The use of standardized FGR definition and measurement protocols enhances reproducibility. However, several limitations should be addressed. The case-control design precludes establishing temporality and causation definitively. Lipid measurements at a single time point (28-34 weeks) might not fully establish longitudinal changes throughout pregnancy. Early pregnancy lipid profiles might provide additional insights into FGR pathogenesis. The study did not assess dietary intake or nutritional status comprehensively, which could influence both maternal lipids and fetal growth. Placental histopathological examination was not systematically performed, limiting insights into placental dysfunction mechanisms. The relatively homogeneous study population may limit generalizability to other ethnic groups with different baseline lipid profiles. Finally, we cannot completely exclude residual confounding from unmeasured variables. Future research should include prospective cohort studies measuring lipid profiles longitudinally from early pregnancy, comprehensive nutritional assessment, placental functional and histological studies, and investigation of genetic factors influencing maternal lipid metabolism and placental lipid transfer. Intervention trials evaluating nutritional strategies to optimize maternal lipid status would provide definitive evidence regarding causality and therapeutic potential.

The study findings demonstrate significant association between maternal lipid profile abnormalities and fetal growth restriction. Women carrying growth-restricted fetuses exhibit substantially lower serum TG, TC, and HDL-cholesterol levels as contrasted with those of appropriately grown fetuses. Maternal hypotriglyceridemia emerged as an independent predictor of FGR, conferring more than three-fold increased risk after controlling for traditional risk factors. The positive correlations between maternal lipid parameters, particularly triglycerides, and birth weight suggest that adequate maternal lipid levels are important for optimal fetal growth. The study highlights the potential role of maternal lipid metabolism in FGR pathogenesis and suggests that impaired maternal-fetal lipid transfer contributes to suboptimal fetal growth. The results support the concept that pregnancy-associated physiological hyperlipidemia serves important adaptive functions beyond mere maternal metabolic changes. Maternal lipid profile assessment could potentially serve as an adjunct screening tool for FGR risk stratification, although prospective validation studies are needed before clinical implementation. Understanding the relationship between maternal lipids and fetal growth has important clinical and public health implications. Nutritional interventions aimed at optimizing maternal lipid status represent a potentially modifiable factor that could contribute to FGR prevention strategies. Future investigations should focus on interventional studies to determine whether nutritional optimization of maternal lipid metabolism can improve fetal growth outcomes in at-risk pregnancies, ultimately reducing the substantial burden of perinatal morbidity and long-term health consequences associated with fetal growth restriction.

1. Gordijn SJ, Beune IM, Thilaganathan B, et al. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333-339. doi: 10.1002/uog.15884 2. Barker DJ, Osmond C, Forsén TJ, et al. Trajectories of growth among children who have coronary events as adults. N Engl J Med. 2005;353(17):1802-1809. doi: 10.1056/NEJMoa044160 3. Murray E, Fernandes M, Fazel M, et al. Differential effect of intrauterine growth restriction on childhood neurodevelopment: a systematic review. BJOG. 2015;122(8):1062-1072. doi: 10.1111/1471-0528.13435 4. Unterscheider J, Daly S, Geary MP, et al. Optimizing the definition of intrauterine growth restriction: the multicenter prospective PORTO Study. Am J Obstet Gynecol. 2013;208(4):290.e1-6. doi: 10.1016/j.ajog.2013.02.007 5. Herrera E, Ortega-Senovilla H. Lipid metabolism during pregnancy and its implications for fetal growth. Curr Pharm Biotechnol. 2014;15(1):24-31. doi: 10.2174/1389201015666140330192345 6. Scifres CM, Catov JM, Simhan HN. The impact of maternal obesity and gestational weight gain on early and mid-pregnancy lipid profiles. Obesity (Silver Spring). 2014;22(3):932-938. doi: 10.1002/oby.20576 7. Lain KY, Catalano PM. Metabolic changes in pregnancy. Clin Obstet Gynecol. 2007;50(4):938-948. doi: 10.1097/GRF.0b013e31815a5494 8. Larqué E, Demmelmair H, Koletzko B. Perinatal supply and metabolism of long-chain polyunsaturated fatty acids: importance for the early development of the nervous system. Ann N Y Acad Sci. 2002;967:299-310. doi: 10.1111/j.1749-6632.2002.tb04285.x 9. Enquobahrie DA, Williams MA, Butler CL, et al. Maternal plasma lipid concentrations in early pregnancy and risk of preeclampsia. Am J Hypertens. 2004;17(7):574-581. doi: 10.1016/j.amjhyper.2004.03.666 10. Jin WY, Lin SL, Hou RL, et al. Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China. BMC Pregnancy Childbirth. 2016;16:60. doi: 10.1186/s12884-016-0852-9 11. Kitajima M, Oka S, Yasuhi I, et al. Maternal serum triglyceride at 24-32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens. Obstet Gynecol. 2001;97(5 Pt 1):776-780. doi: 10.1016/s0029-7844(01)01328-x 12. Koukkou E, Watts GF, Lowy C. Serum lipid, lipoprotein and apolipoprotein changes in gestational diabetes mellitus: a cross-sectional and prospective study. J Clin Pathol. 1996;49(8):634-637. doi: 10.1136/jcp.49.8.634 13. Geraghty AA, Alberdi G, O'Sullivan EJ, et al. Maternal and fetal blood lipid concentrations during pregnancy differ by maternal body mass index: findings from the ROLO study. Am J Clin Nutr. 2017;105(5):1142-1152. doi: 10.3945/ajcn.116.147694 14. Emet T, Ustüner I, Güven SG, et al. Plasma lipids and lipoproteins during pregnancy and related pregnancy outcomes. Arch Gynecol Obstet. 2013;288(1):49-55. doi: 10.1007/s00404-013-2750-y 15. Misra VK, Trudeau S, Perni U. Maternal serum lipids during pregnancy and infant birth weight: the influence of prepregnancy BMI. Obesity (Silver Spring). 2011;19(7):1476-1481. doi: 10.1038/oby.2011.43 16. Haggarty P. Fatty acid supply to the human fetus. Annu Rev Nutr. 2010;30:237-255. doi: 10.1146/annurev.nutr.012809.104742 17. Herrera E, Desoye G. Maternal and fetal lipid metabolism under normal and gestational diabetic conditions. Horm Mol Biol Clin Investig. 2016;26(2):109-127. doi: 10.1515/hmbci-2015-0025 18. Woollett LA. Review: Transport of maternal cholesterol to the fetal circulation. Placenta. 2011;32 Suppl 2:S218-S221. doi: 10.1016/j.placenta.2011.01.011 19. Edison RJ, Berg K, Remaley A, et al. Adverse birth outcome among mothers with low serum cholesterol. Pediatrics. 2007;120(4):723-733. doi: 10.1542/peds.2006-1939 20. Alvarez JJ, Montelongo A, Iglesias A, et al. Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women. J Lipid Res. 1996;37(2):299-308. PMID: 9026528 21. Innis SM. Essential fatty acid transfer and fetal development. Placenta. 2005;26 Suppl A:S70-S75. doi: 10.1016/j.placenta.2005.01.005 22. Lindegaard ML, Damm P, Mathiesen ER, Nielsen LB. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression. J Lipid Res. 2006;47(11):2581-2588. doi: 10.1194/jlr.M600236-JLR200 23. Wadsack C, Desoye G, Hiden U. The feto-placental endothelium in pregnancy pathologies. Wien Med Wochenschr. 2012;162(9-10):220-224. doi: 10.1007/s10354-012-0075-2 24. Porter FD, Herman GE. Malformation syndromes caused by disorders of cholesterol synthesis. J Lipid Res. 2011;52(1):6-34. doi: 10.1194/jlr.R009548 25. Baardman ME, Kerstjens-Frederikse WS, Berger RM, et al. The role of maternal-fetal cholesterol transport in early fetal life: current insights. Biol Reprod. 2013;88(1):24. doi: 10.1095/biolreprod.112.102442 26. Kulkarni SR, Kumaran K, Rao SR, et al. Maternal lipids are as important as glucose for fetal growth: findings from the Pune Maternal Nutrition Study. Diabetes Care. 2013;36(9):2706-2713. doi: 10.2337/dc12-2445 27. Tuckey RC. Progesterone synthesis by the human placenta. Placenta. 2005;26(4):273-281. doi: 10.1016/j.placenta.2004.06.012 28. Wang X, Guan Q, Zhao J, et al. Association of maternal serum lipids at late gestation with the risk of neonatal macrosomia in women without diabetes mellitus. Lipids Health Dis. 2018;17(1):78. doi: 10.1186/s12944-018-0707-7 29. Baksu B, Baksu A, Davas I, et al. Lipoprotein levels in women with pre-eclampsia and in normotensive pregnant women. J Obstet Gynaecol Res. 2005;31(3):277-282. doi: 10.1111/j.1447-0756.2005.00258.x 30. Middleton P, Gomersall JC, Gould JF, et al. Omega-3 fatty acid addition during pregnancy. Cochrane Database Syst Rev. 2018;11(11):CD003402. doi: 10.1002/14651858.CD003402.pub3