Intake and status of iron and fatty acids during pregnancy in association with birth outcomes in women residing in urban South Africa

Abstract

Nutrient requirements increase during pregnancy and women are vulnerable to inadequate nutritional status during this period of rapid foetal growth. Poor dietary intake and nutritional status during pregnancy have been associated with poor birth outcomes and increased risks for noncommunicable diseases in the offspring’s adult life. Low birth weight (LBW) and prematurity are risk factors for disease in later life. It would therefore benefit population health to identify and address predictors of LBW and preterm birth, particularly in low- and middle-income populations. In South Africa, approximately 15% of babies are born LBW and approximately 12% are born preterm. Maternal iron deficiency (ID) has been associated with increased risk for LBW, while poor omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake and status have been associated with premature birth. Iron is important for erythropoiesis, growth and neurodevelopment. PUFAs form an important part of the structural component of cell membranes and play a critical role in cell signalling and are therefore considered essential for optimal foetal growth and development. There are limited data available on the diet as well as the nutritional status of pregnant women in South Africa. A national study on non-pregnant women of child-bearing age has indicated that 15% of women were ID and between 23% and 33% of women were anaemic. No national data exists for fatty acid status, however regional studies on non-pregnant women have indicated that fatty acid status were reflective of dietary intake and that n-3 PUFA intakes are low and n-6 PUFA high. It is probable that the South African iron and PUFA status may contribute to complications during pregnancy, specifically related to length of gestation and birth weight. Therefore, the aim of this research was to assess dietary intake and status of iron and long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy; and to determine associations of maternal iron and LCPUFA status during pregnancy with birth outcomes, in particular gestational age and birth weight, in pregnant women giving birth at Rahima Moosa Mother and Child Hospital (RMMCH) in Johannesburg. A prospective, longitudinal study design was applied. Generally healthy pregnant women (<18 weeks of gestation) were recruited from four primary healthcare clinics in Johannesburg and n=250 were enrolled and followed-up at a tertiary hospital. Participants’ socio-economic data, obstetric history and dietary intake data were collected at study entry. Maternal venous blood was drawn at <18, 22 and 36 weeks of gestation. Additionally, foetal sonography assessments and maternal anthropometrical measurements were performed. Haemoglobin concentrations were determined from whole blood and adjusted for altitude. Iron parameters, serum ferritin and soluble transferrin receptor (sTfR), as well as inflammatory markers were determined using quantitative chemiluminescent multiplex assays. Serum ferritin concentrations were adjusted for inflammation. Red blood cell (RBC) total phospholipid fatty acid composition was determined using gas chromatography. Oral glucose tolerance tests were conducted between 24 and 28 weeks of gestation. At birth, maternal and neonatal health were assessed. Birth weight was obtained using calibrated infant scales and gestational period calculated from first visit sonography data. Logistic and multivariate regression models were used to determine associations between the independent variables (nutrient status) and the outcome variables, namely birth weight and gestational age. Models were adjusted for confounders. Most of the women were of black-African descent (88%) with a median age of 27 (24-32) years. At enrolment the median gestation was 14 (12-16) weeks and the median BMI (26.3 [23.0-30.6] kg/m2) was above a healthy range with 33% of women being overweight and 28% obese. At enrolment, the mean reported iron intake was 19.1 (4.6-46.1) mg per day from foods, which included fortified foods. There was no significant difference in dietary iron intake between the anaemic and non-anaemic women (p=0.45) nor between the ID and non-ID women (p=0.24). Most women (62%) consumed less iron than the Estimated Average Requirement (EAR) (22 mg/day) for women during pregnancy, and two women (1%) had a dietary iron intake above the upper limit (UL) (45 mg) from foods. At enrolment, the prevalence of anaemia, ID and iron deficiency erythropoiesis (IDE) was 28%, 15% and 15%, respectively, which increased significantly with pregnancy progression. There was a high prevalence (60%) of inflammation (CRP >5 mg/L) at enrolment. Multivariable regression analyses showed that anaemia and ID at 22 weeks, as well as IDE at 36 weeks of gestation were associated with higher birth weight (β=168.1; 95% CI: 19.5, 316.7 and β=227.6; 95% CI: 58.4, 396.8 and β=168.7; 95% CI: 27.9, 309.5, respectively). Women in the lowest ferritin quartile at 22 weeks gave birth to babies weighing 312 g (95% CI: 94.8, 528.8) more than those in the highest quartile. In contrast, IDE at 22 weeks was associated with a higher risk for premature birth (OR: 4.62, 95% CI: 1.56, 13.68) and women in lower haemoglobin quartiles at <18 weeks had a shorter gestation by 7 days (β=-6.9, 95% CI: -13.3, -0.6) compared to those in the highest quartile. In terms of the fatty acid intake and status, we found that dietary consumption of n-6 linoleic acid (ALA) was high, while n-3 α-linoleic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake were low. This resulted in a high LA:ALA ratio of 39:1 (28:1-51:1). RBC fatty acid composition changed significantly during pregnancy, however DHA did not decrease in late pregnancy as expected. In fully adjusted models, higher dietary n-6 PUFA and higher RBC arachidonic acid (AA) to EPA ratio were associated with an increased risk for premature birth (OR: 5.03, 95% CI: 1.16, 21.82, p=0.031 and OR: 4.51, 95% CI: 1.29, 15.79). By contrast, higher dietary n-6 PUFA and LA were associated with a lower risk for LBW (OR: 0.05, 95% CI: 0.00, 0.97, p=0.047 and OR: 0.02, 95% CI: 0.00, 0.60, p=0.025). The median birth weight was 3050 (2324-3380) grams and 14% (n=29) of the babies were born with LBW (<2500 g). The median gestational age at birth was 274 (266-282) days and 11% (n=26) of babies were born preterm (<259 days). At early pregnancy, the ID and anaemia prevalence in our sample were comparable to the reported prevalence in non-pregnant women from national surveys. However, anaemia and iron deficiency increased with pregnancy progression, regardless of routine iron supplementation. We suspect that the inflammatory status affected iron bioavailability through the mechanism of increased hepcidin. Noteworthy is that iron deficiency at mid-pregnancy was associated with higher birth weight but increased risk for preterm birth. Similar results were found for women who consumed higher amounts of n-6 PUFA at early pregnancy, namely increased risk for preterm birth and decreased risk for low birth weight. This may be reflective of the interplay between micronutrient status and fatty acid metabolism. Women consumed higher than the recommended n-6 LA and lower than the recommended n-3 ALA and DHA. The change in RBC fatty acid composition with pregnancy progression did not follow the same pattern as shown in literature from other populations. In the context of an urban environment, this sample of generally healthy pregnant women presented with a high prevalence of overweight, obesity and inflammation as well as anaemia and iron-deficiency by late pregnancy. It is important to identify and address nutritional factors that may lower the risk for low birth weight and premature birth to improve the health of future generations in South Africa