Mothers Of Small For Gestational Age Infants Research Articles

Metformin and small for gestational age babies: findings of a randomised placebo-controlled clinical trial of metformin in gestational diabetes (EMERGE).

Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes because of suboptimal glucose management and glucose control and excessive weight gain. Metformin can offset these factors but is associated with small for gestational age (SGA) infants. We sought to identify risk factors for SGA infants, including the effect of metformin exposure on SGA status. In this prespecified secondary analysis of the EMERGE trial, which evaluated the effectiveness of metformin vs placebo in treating GDM and found reduced gestational weight gain and longer time to insulin initiation with metformin use, we included women with a live-born infant and known infant birthweight and gestational age at delivery. We compared the numbers of SGA infants in both groups and explored baseline predictive factors to help identify those at highest risk of delivering an SGA infant. Baseline maternal characteristics were similar between SGA and non-SGA pregnancies. On multivariable-adjusted regression, no baseline maternal variables were associated with SGA status. Mothers of SGA infants were more likely to develop pre-eclampsia or gestational hypertension (18.2% vs 2.0%, p=0.001; 22.7% vs 5.4%, p=0.005, respectively); after multivariable adjustment, pre-eclampsia was positively associated with SGA status). Among SGA pregnancies, important perinatal outcomes including preterm birth, Caesarean delivery and neonatal care unit admission did not differ between the metformin and placebo groups (20.0% vs 14.3%, p=1.00; 50.0% vs 28.6%, p=0.25; 13.3% vs 42.9%, p=0.27, respectively). Pre-eclampsia was strongly associated with SGA infants. Metformin-exposed SGA infants did not display a more severe SGA phenotype than infants treated with placebo. Clinical Trials.gov NCT02980276; EudraCT number: 2016-001644-19.

Invited Commentary: Beyond Barker-Mothers Are the Ones at Risk.

Dr. David Barker hypothesized that low birth weight (LBW) is the result of inadequate fetal nutrition, leading to increased risk ofcardiovascular disease (CVD) in the offspring. This hypothesis has stimulated thousands of reports on low birth weight (LBW) and CVD risk. One problem with this association is that many LBW infants are small because they are preterm, not growth-restricted. A second problem is that maternal CVD risk factors confound the association. In an accompanying article, Lu et al. (Am J Epidemiol. 2023;192(6):866-877) address both concerns. Using population data from Sweden and Denmark, the authors estimated CVD incidence among offspring born small for gestational age (SGA). The smallest 3% had a CVD hazard ratio of 1.44 (95% confidence interval: 1.38, 1.51). Even this moderate risk mostly evaporated in sibship analysis, which controlled for unmeasured maternal CVD risk factors (hazard ratio = 1.11, 95% confidence interval: 0.99, 1.25). The risk highlighted by Barker is negligible, especially when compared with a more urgent health issue-cardiovascular risk in women with pregnancy complications. Mothers of SGA infants have up to a 3-fold CVD risk, and mothers with preeclampsia and preterm delivery have up to a 9-fold risk. Pregnancy complications thus provide an early marker of a woman's propensity to develop CVD, and perhaps an opportunity for early intervention. From a public health perspective, Barker's hypothesis about CVD risk in LBW offspring is less compelling than the question of CVD risk among mothers with pregnancy complications. This article is part of a Special Collection on ABC.

Comparison of Breast Milk Compositions Among Mothers Delivering Small-for-Gestational Age, Appropriate-for-Gestational Age, and Large-for-Gestational Age Infants.

The aim of this study was to compare the breast milk compositions of mothers who delivered babies in three different birth weight categories. We collected 75 breast milk samples from mothers of small-for-gestational age (SGA), appropriate-for-gestational age (AGA), and large-for-gestational age (LGA) term infants (25 per group) on the 11th-28th day postpartum using a manual or electric breast pump. Homogenized samples were analyzed using a mid-infrared human milk analyzer within 2 hours of collection, and protein, carbohydrate (CHO), fat, and energy levels were compared. Of 75 participants (median maternal age: 29 years), there was a significant difference in maternal body mass index (BMI), gestational age, and birth weight among the three groups. However, we found no significant variation in breast milk true protein, crude protein, fat, or energy. The CHO composition of breast milk in mothers of SGA infants (7.1 g/100 mL, range: 6.6-7.3 g/100 mL) was significantly lower than that in the AGA (7.3 g/100 mL, range: 7.1-7.5 g/100 mL) and LGA (7.2 g/100 mL, range: 6.7-7.4 g/100 mL) groups. After post hoc multiple comparison, only CHO levels between the SGA and AGA groups were significantly different (p = 0.025), whereas no significant correlation was found between maternal BMI, gestational age, and CHO. The CHO component in breast milk from mothers of SGA infants was significantly lower compared with the AGA and LGA groups, but with no clinical significance. Breast milk compositions of mothers of LGA infants were comparable to those of SGA and AGA infants. Therefore, fetal growth status does not significantly influence maternal breast milk nutrients.

Increased docosahexaenoic acid and n-3 polyunsaturated fatty acids in milk from mothers of small for gestational age preterm infants

The study aimed to test whether or not milk fatty acid composition in mothers of small for gestational age (SGA) infants is similar to that in mothers of adequate for gestational age (AGA) infants. Thirty three mothers of SGA preterm infants and 66 mothers of AGA preterm infants were included. Milk and plasma fatty acids were analyzed using capillary gas chromatography. Milk DHA (0.68 ± 0.37 vs. 0.44 ± 0.24; p < 0.01) was higher and n-6:n-3 PUFA ratio (12.0 ± 4.64 vs. 16.0 ± 6.32; p < 0.05) was lower in mothers of SGA infants. Plasma ARA and DHA were increased in mothers of SGA infants and decreased in their infants. Milk ARA or DHA was positively related to the correspondent fatty acid in plasma (r = 0.374, p = 0.010 for ARA and r = 0.690, p < 0.001 for DHA). Breast milk in mothers of preterm infants born SGA is enriched in DHA and n-3 PUFA. Breastfeeding SGA preterm infant with own mother's milk is recommended.

Fatty acids composition of human milk fed to small for gestational age infants

Objectives: To test the null hypothesis that mothers of asymmetric small for gestational age (SGA) infants produce milk with fatty acids composition similar to that of lactating mothers of appropriate-for-gestational-age (AGA) infants.Methods: We obtained human milk (HM) from 2 groups of lactating volunteers that gave birth to asymmetric SGA (study group) or AGA infants (control group). Each mother was asked to contribute by manual expression at least one of 3 samples: first 72 hours after labor (colostrum), day 2-7 postpartum (transitional milk) and 14 days post partum (mature milk). After lipid extraction using Folch's cold-extraction procedure fatty acids were analyzed using gas chromatography.Results: A total of 108 samples were obtained in 60 women. In univariate analysis, there were no significant differences in any of the fatty acids concentrations examined between groups. This remained true when timing of the sample (colostrum, transitional or mature milk) or gestational age were introduced as confounders in analysis of variance (general linear model).Conclusion: Fatty acid composition of human milk is not affected by whether or not the infant was fetal growth restricted. We suggest that mothers of SGA infants may be reassured about the fat quality of their milk.

Breast milk fat content of mothers to small-for-gestational-age infants.

Little is known about the composition of human milk (HM) expressed by mothers of asymmetrically growth-restricted infants. To test the null hypothesis that lactating mothers of small-for-gestational-age (SGA) infants produce milk with fat content similar to that of lactating mothers of infants whose growth is appropriate for gestational age (AGA). Fifty-six lactating mothers of newborns (26 SGA and 30 AGA) were recruited within the first 3 days of delivery. Creamatocrit (CMT) levels in HM were measured at 72 h, 7 days and 14 days postdelivery in capillary tubes after centrifugation at 9000 r.p.m. for 5 min. The groups did not differ in terms of maternal age, body mass index, gestational age (GA), pregnancy weight gain and parity. They differed significantly in terms of infant's birth weight by design. The mean CMT levels at the three time points were similar for the two groups. This remained true when timing of the sample (colostrum, transitional, mature milk) was introduced as a confounder in the analysis of variance (general linear model). Fat content of HM is not affected by fetal growth status. We suggest that mothers of SGA infants may be reassured that their milk contains adequate amount of fat that is appropriate for the growth of their infants.

Outcomes of Small for Gestational Age Infants Born at &lt;27 Weeks' Gestation

To determine whether small for gestational age (SGA) infants born at <27 weeks gestational age (GA) are at increased risk for mortality, morbidity, and growth and neurodevelopmental impairment at 18-22 months corrected age. This was a retrospective cohort study from National Institute of Child Health and Human Development Neonatal Research Network's Generic Database and Follow-Up Studies. Infants born at <27 weeks GA between January 2006 and July 2008 were included. SGA was defined as birth weight <10th percentile for GA based on Olsen growth curves. Infants with birth weight ≥ 10th percentile for GA were classified as non-SGA. Maternal and infant characteristics, neonatal outcomes, and neurodevelopmental data were compared in SGA and non-SGA infants. Neurodevelopmental impairment was defined as any of the following: cognitive score <70 on the Bayley Scales of Infant Development III, moderate or severe cerebral palsy, bilateral hearing loss (with and without amplification), or blindness (bilateral vision <20/200). Logistic regression analysis was applied to evaluate the associations between SGA status and death or neurodevelopmental impairment. The SGA group comprised 385 infants; the non-SGA group, 2586 infants. Compared with mothers of non-SGA infants, mothers of SGA infants were more likely to have a high school education, prenatal care, cesarean delivery, pregnancy-induced hypertension, and antenatal corticosteroid exposure. Compared with non-SGA infants, SGA infants had higher mortality and were more likely to have postnatal growth failure, prolonged mechanical ventilation, and postnatal steroid use. SGA status was associated with increased risk of death or neurodevelopmental impairment (OR, 3.91; 95% CI, 2.91-5.25; P < .001). SGA status in infants born at <27 weeks GA is associated with an increased likelihood of postnatal steroid use, mortality, growth failure, and neurodevelopmental impairment at 18-22 months corrected age.

Comparison of perinatal outcomes in small‐for‐gestational‐age infants classified by population‐based versus customised birth weight standards

The objective of this study was to derive a customised birth weight standard curve in our institute and to compare the perinatal outcomes of small-for-gestational-age (SGA) births classified by population-based versus customised birth weight standards. We surveyed 9052 normal singleton deliveries and generated customised standards by adjusting for maternal characteristics and neonatal gender. We compared adverse perinatal outcomes between SGA and non-SGA births classified by both standards. According to the population-based standards, mothers of SGA infants were younger, thinner and shorter and had higher rates of nulliparity and female births. We adjusted for these maternal characteristics and neonatal gender in our customised standards. Multivariate analysis revealed that there were no differences in neonatal composite morbidity between the standards. However, infants classified as SGA by the customised standards showed a significantly higher rate of neonatal intensive care unit (NICU) admission than those classified by the population-based standards. Our study showed that customised SGA made no significant differences in neonatal composite morbidity, only a modest increase in NICU admission rate compared to population-based standard. To clarify the association of adverse perinatal outcomes with customised SGA, larger studies are required.

Potential role for elevated maternal enzymatic antioxidant status in Andean protection against altitude-associated SGA

Oxidative stress has been implicated in the uteroplacental ischemia characteristic of preeclampsia and small-for-gestational-age (SGA) birth, both of which are more common at high (>2500 m) vs low altitude. Since Andeans are protected relative to Europeans from the altitude-associated rise in SGA, we asked whether alterations in maternal antioxidant status or oxidative stress contributed to their protection. Enzymatic antioxidant (erythrocyte catalase and superoxide dismutase [SOD]) activity and a plasma marker of lipid peroxidation (8-iso-PGF2α) were measured during pregnancy and in the non-pregnant state in Andean or European residents of low (400 m) or high altitude (3600–4100 m). Pregnancy and altitude increased catalase and/or SOD activity to a greater extent in Andeans than Europeans. 8-iso-PGF2α levels were independent of altitude and pregnancy. SOD was lower in mothers of SGA infants at weeks 20 and 36. Our findings are consistent with the possibility that elevated enzymatic antioxidant activity contributes to Andean protection against altitude-associated SGA.

Prediction of pre-eclampsia in early pregnancy by estimating the spot urinary albumin: creatinine ratio using high-performance liquid chromatography

To establish whether a spot urinary albumin: creatinine ratio (ACR) measured before 20 weeks of gestation can predict subsequent pre-eclampsia when urinary albumin is measured by high-performance liquid chromatography (HPLC). Prospective exploratory study. Antenatal clinic in a tertiary teaching hospital, Victoria, Australia. A cohort of 265 women with a singleton pregnancy, normal renal function, and no evident proteinuria, attending antenatal clinics between 12 and 20 weeks of gestation. The ACR was determined from a mid-stream urine (MSU) sample taken between 17 and 20 weeks of gestation. Intact urinary albumin was determined by HPLC; creatinine was measured by modified Jaffe's method. Pre-eclampsia (primary); gestational hypertension, small for gestational age (SGA), gestational diabetes mellitus, gestational age at delivery, and prematurity (secondary). The median ACR was 28 mg/mmol (IQR 16-46 mg/mmol). Women who subsequently developed pre-eclampsia had a significantly higher ACR (median 50 mg/mmol; IQR 33-90 mg/mmol) compared with women suffering from gestational hypertension (median 27 mg/mmol; IQR 8-35 mg/mmol), and compared with unaffected women (median 28 mg/mmol; IQR 16-46 mg/mmol). Mothers of SGA infants also had a significantly higher median ACR. By ROC analysis, the optimum ACR to predict pre-eclampsia was 35.5 mg/mmol: the relative risk of developing pre-eclampsia in women with a urinary ACR ≥ 35.5 mg/mmol was 7.8 times more than in those with a urinary ACR < 35.5 mg/mmol. When urinary albumin is measured by HPLC, spot urinary ACR values are higher in early uncomplicated pregnancy compared with previously reported conventional methods. When measured early in the second trimester, an ACR ≥ 35.5 mg/mmol predicted pre-eclampsia well before the onset of clinical manifestations.

Body Composition of Women with Newborns Who Are Small for Gestational Age

Background: The relationship between maternal and placental hemodynamic disorders and fetal growth is well known, but few studies have evaluated a link between maternal extracellular water (EW) and newborn birth weight. Objective: To identify the characteristics of body composition (BC) of women with small for gestational age (SGA) newborns, and to determine the relationship between maternal EW and birth weight of the baby. Methods: We studied maternal BC using multifrequency bioelectric impedance in the second and third trimesters of pregnancy. Newborns with weight below the 10th percentile were classified as SGA; those with weights between the 10th and 90th percentiles as appropriate for gestational age (AGA), and large for gestational age (LGA) were those with weights above the 90th percentile. Results: We studied 460 women and their BC varied depending on whether their newborns were SGA, AGA or LGA. EW was lower in the mothers of SGA (11 ± 2 l) compared to AGA (12 ± 3 l) newborns (p < 0.01). We identified a significant relationship (p < 0.01) between maternal EW in the second trimester and the weight of the newborn, β = 43 (95% CI 27–58). Conclusion: BC of women whose newborns are SGA differs significantly from that of women whose newborns are AGA, a result which suggests that the mothers of SGA infants may have a disordered hemodynamic state during the second trimester of pregnancy.

Maternal nutritional risk factors for small for gestational age babies in a developed country: a case-control study

Aims: To assess the effect of maternal diet during pregnancy on the risk of delivering a baby who is small for gestational age (SGA). Methods: Case-control study of 844 cases...

High caffeine consumption in the third trimester of pregnancy: gender-specific effects on fetal growth.

It has been suggested that a high caffeine intake in pregnancy may be a risk factor for fetal growth retardation. We have tested this hypothesis in a population-based case-control study. Caffeine intake among 111 mothers of small-for-gestational-age (SGA) infants (56 boys, 55 girls) was compared with the intake among 747 mothers of non-SGA infants (368 boys, 379 girls). Food records for 3 days were collected in the second (week 17-20) and in the third (week 33) trimester, and caffeine intake from coffee, tea, soft drinks and chocolate was calculated and dichotomised as low or high, based upon the median value. Mothers of SGA infants had higher mean intake of caffeine [281 +/- 210 (SD) mg/day] in the third trimester than mothers of non-SGA infants (212 +/- 150 mg/day; P < 0.001). The risk of SGA birth was nearly doubled if the mother had a high rather than a low caffeine intake in the third trimester [odds ratio (OR) 1.8; 95% confidence intervals (CI) 1.2, 2.5]. The increased risk was mainly found in boys (OR 2.8; 95% CI 1.5, 5.2), and not in girls (OR 1.2; 95% CI 0.7, 2.1). The increased risk for boys persisted after adjustment for cigarette smoking alone, or for smoking and various other SGA risk factors together. Our results suggest that a high caffeine intake in the third trimester may be a risk factor for fetal growth retardation, in particular if the fetus is a boy.

Risk factors for small-for-gestational-age babies: The Auckland Birthweight Collaborative Study.

This case-control study determined whether internationally recognized risk factors for small-for-gestational-age (SGA) term babies were applicable in New Zealand. All babies were born at 37 or more completed weeks of gestation in one of three hospitals in Auckland. Cases weighed less than the sex specific 10th percentile for gestational age at birth, and controls (appropriate-for-gestational-age (AGA)) were a random selection of heavier babies. Information was collected by maternal interview and from obstetric databases. Information from 1714 completed interviews (844 SGA and 870 AGA) was available for analysis. Computerized obstetric records were available for 1691 of the 1701 women who consented to such access. In a multivariate analysis allowing for sex, gestational age at birth, social class and other potential confounders, mothers who smoked had a significantly increased risk of an SGA baby (adjusted OR 2.41; 95% CI 1.78-3.28), as did primiparous mothers (adjusted OR 1.34; 95% CI 1.03-1.73), mothers of Indian ethnicity (adjusted OR 3.22; 95% CI 1.95-5.30), women with pre-eclamptic toxaemia (adjusted OR 2.42; 95% CI 1.08-5.40) and those with pre-existing hypertension toxaemia (adjusted OR 5.49; 95% CI 1.81-16.71). Mothers of SGA infants were shorter (P < 0.001) and reported lower prepregnancy body weights (P < 0.001) than mothers of AGA infants. The population attributable fraction for smoking suggests that up to 18% of SGA infants born in the ABC Study could be related to maternal smoking. Risk factors associated with SGA births in other countries are also important in New Zealand. Smoking in pregnancy is an important and potentially modifiable behaviour, and efforts to decrease the number of women who smoke during pregnancy should be encouraged.