Associations of Maternal Retinal Vasculature with Subsequent Fetal Growth and Birth Size

Objective

We aimed to study the maternal retinal microvasculature at mid-trimester and its relationship with subsequent fetal growth and birth size.

Methods

We recruited 732 pregnant women aged 18-46 years in the first trimester with singleton pregnancies. All had retinal photography and fetal scan performed at 26-28 weeks gestation, and subsequent fetal scan at 32-34 weeks gestation. Infant anthropometric measurements were done at birth. Retinal microvasculature was measured using computer software from the retinal photographs.

Results

In multiple linear regression models, each 10 μm narrowing in maternal retinal arteriolar caliber was associated with decreases of 1.36 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.50 mm and 2.30 mm in infant head circumference and birth length at delivery, respectively. Each standard deviation decrease in maternal retinal arteriolar fractal dimension was associated with decreases of 1.55 mm in fetal head circumference at 32-34 weeks gestation, as well as decreases of 1.08 mm and 46.42 g in infant head circumference and birth weight at delivery, respectively.

Conclusions

Narrower retinal arteriolar caliber and a sparser retinal vascular network in mothers, reflecting a suboptimal uteroplacental microvasculature during mid-pregnancy, were associated with poorer fetal growth and birth size.     

A common genetic variant at 15q25 modifies the associations of maternal smoking during pregnancy with fetal growth: the generation R study

Objective

Maternal smoking during pregnancy is associated with fetal growth retardation. We examined whether a common genetic variant at chromosome 15q25 (rs1051730), which is known to be involved in nicotine metabolism, modifies the associations of maternal smoking with fetal growth characteristics.

Methods

This study was performed in 3,563 European mothers participating in a population-based prospective cohort study from early pregnancy onwards. Smoking was assessed by postal questionnaires and fetal growth characteristics were measured by ultrasound examinations in each trimester of pregnancy.

Results

Among mothers who did not smoke during pregnancy (82.9%), maternal rs1051730 was not consistently associated with any fetal growth characteristic. Among mothers who continued smoking during pregnancy (17.1%), maternal rs1051730 was not associated with head circumference. The T-allele of maternal rs1051730 was associated with a smaller second and third trimester fetal femur length [differences −0.23 mm (95%CI −0.45 to −0.00) and −0.41 mm (95%CI −0.69 to −0.13), respectively] and a smaller birth length [difference −2.61 mm (95%CI −5.32 to 0.11)]. The maternal T-allele of rs1051730 was associated with a lower third trimester estimated fetal weight [difference −33 grams (95%CI −55 to −10)], and tended to be associated with birth weight [difference −38 grams (95%CI −89 to 13)]. This association persisted after adjustment for smoking quantity.

Conclusions

Our results suggest that maternal rs1051730 genotype modifies the associations of maternal smoking during pregnancy with impaired fetal growth in length and weight. These results should be considered as hypothesis generating and indicate the need for large-scale genome wide association studies focusing on gene – fetal smoke exposure interactions.     

Switching maternal dietary intake at the end of the first trimester has profound effects on placental development and fetal growth in adolescent ewes carrying singleton fetuses.

The aim was to investigate whether placental growth and hence pregnancy outcome could be altered by switching adolescent dams from a high to a moderate nutrient intake, and vice-versa, at the end of the first trimester. Embryos recovered from adult ewes inseminated by a single sire were transferred in singleton to peripubertal adolescents. After transfer, adolescent ewes were offered a high (H, n = 33) or moderate (M, n = 32) level of a diet calculated to promote rapid or moderate maternal growth rates, respectively. At Day 50 of gestation, half the ewes had their dietary intakes switched, yielding 4 treatment groups: HH, MM, HM, and MH. A subset of ewes were killed at Day 104 of gestation to determine maternal body composition in relation to growth of the products of conception. Maternal body composition measurements revealed that the higher live weight in the high-intake dams was predominantly due to an increase in body fat deposition, with a less pronounced increase in body protein. At Day 104, HH and MH groups (high intake during second trimester) compared with MM and HM groups (moderate intake during second trimester) had a lower (p < 0.002) total fetal cotyledon weight; but fetal weight, conformation, and individual organ weights were not significantly influenced by maternal dietary intake. In ewes delivering live young at term, a high plane of nutrition from the end of the first trimester (HH and MH groups) compared with moderate levels (MM and HM groups) was associated with a reduction in gestation length (p < 0.009), total placental weight (p < 0.002), total fetal cotyledon weight (p < 0.001), and mean fetal cotyledon weight per placenta (p < 0.001). Fetal cotyledon number was dependent on maternal dietary intake during the first trimester only and was lower (p < 0.007) in HH and HM ewes compared to MM and MH ewes. The inhibition of fetal cotyledon growth in HH and MH groups was associated with a major decrease (p < 0.001) in lamb birth weight at term relative to the MM and HM groups. Thus, reducing maternal dietary intake from a high to a moderate level at the end of the first trimester stimulates placental growth and enhances pregnancy outcome, and increasing maternal dietary intake at this time point has a deleterious effect on placental development and fetal growth.     

Maternal age and parity influence ultrasonographic measurements of fetal growth in Dutch Warmblood mares

Ultrasonographic examination of the equine fetus in mid-late gestation is usually performed only if there are concerns about fetal or maternal health. Even then it is difficult to determine whether development is ‘normal’ for gestational age because the reference values include considerable error margins. This study examined maternal factors that influence fetal growth with the aim of producing more precise late gestation fetal growth curves for Dutch Warmblood horses. Fetal development was monitored at 2-week intervals from day 100 of gestation until term in 32 mares ranging from 4 to 18 years in age; seven of the mares were primiparous. Transrectal and/or transabdominal ultrasonographic measurement of the fetal eye orbit, cranium, aorta, heart rate and of the combined thickness of uterus and placenta (CTUP) were performed using a portable ultrasound machine equipped with 6 MHz linear and 3.5 MHz curved array probes.During days 100–250 of gestation, the CTUP was thicker in primiparous than multiparous mares (p < 0.05). After day 220 the maximum cross-sectional area, but not diameter, of both the eye orbit and cranium were also greater in primiparous than multiparous mares (p < 0.05). Fetal aorta diameter was not influenced by parity but was affected by maternal age, being smaller in mares ≥15 years of age than younger animals (p < 0.05). Only biparietal cross-sectional surface area and aorta diameter increased linearly throughout late gestation. However, even allowing for the effects of parity and maternal age, the late gestational variation in fetal size is such that serial measurements may be required to definitively identify abnormal development.     

Prenatal Exposure to Arsenic and Its Effects on Fetal Development in the General Population of Dalian

To evaluate prenatal exposure to arsenic in the general population and its effects on birth size, we conducted a cross-sectional study in Dalian, China. Arsenic concentration in maternal and cord blood was detected by inductively coupled plasma-mass spectrometry and its effects on birth size were analyzed by multivariate analysis and multiple linear regression analysis. Arsenic concentrations in cord blood were significantly lower than those in maternal blood. A significant positive correlation was shown between maternal and cord blood arsenic concentrations. Maternal arsenic concentration was negatively associated with birth weight, height and chest circumference, and fetal arsenic concentration was negatively associated with head circumference. Our results indicate that arsenic exposure at environmental levels in uterus may pose adverse effects on fetal development.     

The influence of fetoabdominal tissues on fetal ECGs and MCGs

Both fetal electrocardiography and fetal magnetocardiography are influenced by the volume conduction within the abdomen of the pregnant woman. In this paper, various models are used to simulate this influence. Such models are helpful to determine where to attach electrodes at the maternal abdomen in case fetal ECGs are measured and where to position the magnetocardiograph in case fetal MCGs are measured. Another goal is to assess the influence of individual differences, such as the amount of amniotic fluid. Seven models based on MR-images have been created, four for the third trimester of gestation, with the fetus in left occiput position, and three for the second trimester. The models consist of four compartments; the fetus, the vernix caseosa, the amniotic fluid, and the remainder of the maternal abdomen. It turns out that individual differences have a large impact on the fetal MCG and that the best measurement positions are expected over the centre of the abdomen near the fetal heart. The fetal ECG is dependent on the vernix caseosa and when this layer is present, the fetal ECG is best measured by two electrodes, one over the fetal mouth and the other over the bottom of the fetus.     

Maternal corticotropin-releasing hormone levels during pregnancy and offspring adiposity

Objective: Animal models suggest that fetal exposure to glucocorticoids can program adiposity, especially central adiposity, later in life. We examined associations of maternal corticotropin‐releasing hormone (CRH) levels in the late 2nd trimester of pregnancy, a marker of fetal glucocorticoid exposure, with child adiposity at age 3 years. Research Methods and Procedures: We analyzed data from 199 participants in Project Viva, a prospective cohort study of pregnant women and their children, At age 3 years, the main outcomes were age‐sex‐specific BMI z score and the sum of subscapular (SS) and triceps (TR) skinfold thicknesses to represent overall adiposity, and ratio of SS to TR (SS:TR) to represent central adiposity. Results: Mean (standard deviation) maternal 2nd trimester log CRH was 4.94 (0.56) pg/mL. At age 3, mean (standard deviation) for BMI z score was 0.52 (1.02); for SS + TR, 16.51 (3.94) mm; and for SS:TR, 0.67 (0.17). Log CRH was mildly inversely correlated with birth weight (r = ?0.08), chiefly because of its association with length of gestation (r = ?0.21) rather than fetal growth (r = ?0.004). After adjustment for sociodemographic factors, maternal smoking, BMI, and gestational weight gain, fetal growth, length of gestation, breastfeeding duration, and (for SS:TR only) child's 3‐year BMI, each increment of 1 unit of log CRH was associated with a reduction in BMI z score [?0.43; 95% confidence interval (CI), ?0.73, ?0.14; p = 0.004] and possible reduction in SS + TR (?1.10; 95% CI, ?2.33, 0.14; p = 0.08). In contrast, log CRH was associated with higher SS:TR (0.07; 95% CI, 0.02, 0.13; p = 0.007). Discussion: Fetal exposure to glucocorticoids, although associated with an overall decrease in body size, may cause an increase in central adiposity.     

Maternal urinary cadmium concentrations in early pregnancy in relation to prenatal and postpartum size of offspring

BackgroundThe impacts of environmental cadmium (Cd) exposure on birth size parameters including weight, length and head circumference (HC) have been reported in multiple studies. However, little remains known of the impacts of maternal Cd exposure during pregnancy on size during in utero development and during early childhood. The aim of this study was to comprehensively investigate impacts of maternal Cd exposure during pregnancy on the size of offspring in utero (from 24 weeks pregnancy) until six months of age.MethodsPregnant mothers were recruited as part of an ongoing prospective birth cohort study based in Guangdong, China. Maternal urine samples were collected in the first and third trimesters of pregnancy, in which Cd concentrations were measured by inductively couple plasma mass spectrometry (ICPMS). In utero size indicators at 24 and 32 week of gestation, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and HC were derived from ultrasound examinations. Anthropometric measures of weight, height and HC at birth and one, three and six months of age were also collected. Associations of size measures at the various time points with maternal urinary Cd concentrations were assessed using linear regression models.ResultsThe median urinary Cd concentration was 1.00 and 0.98 μg/g creatinine in the first and third trimesters respectively. In univariate analysis, increased maternal Cd levels in the first trimester were associated with decreased HC (-0.17 cm/ug/g urinary Cd) at birth, and the association was particularly pronounced among males (-0.30 cm/ug/g urinary Cd). First trimester Cd exposure was also found to be significantly associated with decreased infant weight at three and six months of age among girls (−101 g/ug/g and −97 g/ug/g urinary Cd, respectively). Associations of similar magnitude were observed after adjustment for various maternal factors. No significant associations were observed with infant size measures or with measures of Cd in the third trimester.ConclusionsOur detailed study suggests that the first trimester is particularly critical window of susceptibility to sex-specific effects of Cd on size parameters at birth, with some effects persisting to six months of age. These compelling sex-dependent effects on HC and body weight warrant future studies examining longer-term health effects of pregnancy-related Cd exposures.     

A Bayesian Latent Variable Mixture Model for Longitudinal Fetal Growth

Summary Fetal growth restriction is a leading cause of perinatal morbidity and mortality that could be reduced if high‐risk infants are identified early in pregnancy. We propose a Bayesian model for aggregating 18 longitudinal ultrasound measurements of fetal size and blood flow into three underlying, continuous latent factors. Our procedure is more flexible than typical latent variable methods in that we relax the normality assumptions by allowing the latent factors to follow finite mixture distributions. Using mixture distributions also permits us to cluster individuals with similar observed characteristics and identify latent classes of subjects who are more likely to be growth or blood flow restricted during pregnancy. We also use our latent variable mixture distribution model to identify a clinically meaningful latent class of subjects with low birth weight and early gestational age. We then examine the association of latent classes of intrauterine growth restriction with latent classes of birth outcomes as well as observed maternal covariates including fetal gender and maternal race, parity, body mass index, and height. Our methods identified a latent class of subjects who have increased blood flow restriction and below average intrauterine size during pregnancy. These subjects were more likely to be growth restricted at birth than a class of individuals with typical size and blood flow.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

The effect of maternal undernutrition on the growth and development of the guinea pig placenta.

Fetal growth is known to be correlated with the size of the placenta and the exchange surface area. Reduction in the growth of the materno-fetal exchange surface areas may be a mechanism by which the effects of maternal undernutrition on fetal growth are mediated. In the compact placenta of the guinea pig the exchange surface is equivalent to the peripheral labyrinth. The effect of a 40% reduction in maternal feed intake on the growth of the peripheral labyrinth was investigated in pregnant guinea pigs between gestational days 25 and 65. Fetal and placental weights were significantly reduced in the last trimester by 32% and 38% respectively (P < 0.01). Placental efficiency in early gestation was significantly impaired in restricted animals but equivalent to ad lib. fed controls by the last trimester. The volume of the peripheral labyrinth increased as a percentage of the total placental volume with gestational age. Restricted placentae tended to be composed of a smaller volume of peripheral labyrinth tissue in early gestation. It is suggested that maternal undernutrition results in an impaired or delayed expansion of the peripheral labyrinth in early gestation causing a reduction in placental efficiency. By the last trimester the weight of the peripheral labyrinth of restricted animals was reduced by 33% (P < 0.05). The weight of the peripheral labyrinth was also significantly correlated with fetal weight is limited by the size of the peripheral labyrinth in the later stages of gestation.     

The Role of Maternal Stress in Early Pregnancy in the Aetiology of Gastroschisis: An Incident Case Control Study

Objective

The incidence of gastroschisis, a congenital anomaly where the infant abdominal wall is defective and intestines protrude from the abdominal cavity, is increasing in many countries. The role of maternal stress in some adverse birth outcomes is now well established. We tested the hypothesis that major stressful life events in the first trimester are risk factors for gastroschisis, and social support protective, in a case-control study in the United Kingdom.

Methods

Gastroschisis cases and three controls per case (matched for maternal age) were identified at routine 18-20 week fetal anomaly ultrasound scan, in 2007-2010. Face to face questionnaire interviews were carried out during the antenatal period (median 24 weeks gestation) asking about serious stressful events and social support in the first trimester. Data were analysed using conditional logistic regression.

Results

Two or more stressful life events in the first trimester (adjusted OR 4.9; 95% CI 1.2-19.4), and moving address in the first trimester (aOR 4.9; 95% CI 1.7-13.9) were strongly associated with risk of gastroschisis, independent of behavioural risk factors including smoking, alcohol, and poor diet. Perceived availability of social support was not associated with reduced risk of gastroschisis (aOR 0.8; 95% CI 0.2-3.1).

Conclusions

Stressful maternal life events in the first trimester of pregnancy including change of address were strongly associated with a substantial increase in the risk of gastroschisis, independent of stress related high risk behaviours such as smoking, alcohol consumption and poor diet. This suggests that stress pathways are involved in the aetiology of gastroschisis.     

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: Prospective results from a folate-replete population

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.Key words: DNA methylation, pregnancy, cord blood, maternal diet, cadmium     

Correlation between maternal inflammatory markers and fetomaternal adiposity

Outside pregnancy, both obesity and diabetes mellitus are associated with changes in inflammatory cytokines. Obesity in pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or fetal macrosomia. The objective of this study was to determine the correlation between maternal cytokines and fetomaternal adiposity in the third trimester in women where the important confounding variable GDM had been excluded. Healthy women with a singleton pregnancy and a normal glucose tolerance test at 28weeks gestation were enrolled at their convenience. Maternal cytokines were measured at 28 and 37weeks gestation. Maternal adiposity was assessed indirectly by calculating the Body Mass Index (BMI), and directly by bioelectrical impedance analysis. Fetal adiposity was assessed by ultrasound measurement of fetal soft tissue markers and by birthweight at delivery. Of the 71 women studied, the mean maternal age and BMI were 29.1years and 29.2kg/m(2) respectively. Of the women studied 32 (45%) were obese. Of the cytokines, only maternal IL-6 and IL-8 correlated with maternal adiposity. Maternal TNF-α, IL-β, IL-6 and IL-8 levels did not correlate with either fetal body adiposity or birthweight. In this well characterised cohort of pregnant non-diabetic women in the third trimester of pregnancy we found that circulating maternal cytokines are associated with maternal adiposity but not with fetal adiposity.     

Brief communication: Fecal androgen excretion and fetal sex effects during gestation in wild Assamese macaques (Macaca assamensis)

In placental mammals, pregnancy usually is associated with an increase in maternal androgens, which may significantly impact fetal growth and differentiation, and affect postnatal development and behavior. Owing to their slow life histories and challenging social conditions, determination of maternal androgens and potential interference effects of fetal androgen production are of particular interest in wild primates. However, androgen production has been rarely investigated in wild female primates, and studies on maternal androgens during gestation in particular often do not span the entire pregnancy. Here, we characterize fecal androgen production throughout gestation in wild Assamese macaques (Macaca assamensis) using noninvasive hormone analysis and, furthermore, examine fetal sex effects on maternal androgen excretion. A total of 207 fecal samples were analyzed from seven females for concentrations of immunoreactive epiandrosterone (iEA). Fecal iEA concentrations, as predicted based on cercopithecine blood-serum patterns, increased during early gestation and were significantly higher during the first trimester compared with preconception concentrations and those recorded during later stages of gestation. Further, during the third trimester, male-carrying mothers showed significantly higher iEA concentrations compared with female-carrying mothers. This first characterization of fecal androgen excretion during gestation in Assamese macaques indicates both a maternal and fetal effect on androgen production. Although our sample size is small, our results, nevertheless, provide the basis for assessing potential influences of maternal androgens on postnatal offspring development and behavior.     

Cardiovascular mortality in twins and the fetal origins hypothesis.

The intrauterine growth patterns for twins are characterized by normal development during the first two trimesters and reduced growth during the third trimester. According to the fetal origins hypothesis this growth pattern is associated with risk factors for cardiovascular morbidity and mortality. We studied cause-specific mortality of 19,986 Danish twin individuals from the birth cohorts 1870-1930 followed from 1952 through 1993. Despite the large sample size and follow-up period we were not able to detect any difference between twins and the general population with regard to all-cause mortality or cardiovascular mortality. Hence, the intrauterine growth retardation experienced by twins does not result in any "fetal programming" of cardiovascular diseases. There is still an important role for twins (and other sibs) to play in the testing of the fetal origins hypothesis, namely in studies of intra-pair differences, which can assess the role of genetic confounding in the association between fetal growth and later health outcome.     

Maternal Prenatal Positive Affect,Depressive and Anxiety Symptoms and Birth Outcomes: The PREDO Study

Background

We investigated whether maternal prenatal emotions are associated with gestational length and birth weight in the large PREDO Study with multiple measurement points of emotions during gestation.

Methods

Altogether 3376 pregnant women self-assessed their positive affect (PA, Positive and Negative Affect Schedule) and depressive (Center for Epidemiologic Studies Depression Scale, CES-D) and anxiety (Spielberger State Anxiety Scale, STAI) symptoms up to 14 times during gestation. Birth characteristics were derived from the National Birth Register and from medical records.

Results

One standard deviation (SD) unit higher PA during the third pregnancy trimester was associated with a 0.05 SD unit longer gestational length, whereas one SD unit higher CES-D and STAI scores during the third trimester were associated with 0.04–0.05 SD unit shorter gestational lengths (P-values ≤ 0.02), corresponding to only 0.1–0.2% of the variation in gestational length. Higher PA during the third trimester was associated with a significantly decreased risk for preterm (< 37 weeks) delivery (for each SD unit higher positive affect, odds ratio was 0.8-fold (P = 0.02). Mothers with preterm delivery showed a decline in PA and an increase in CES-D and STAI during eight weeks prior to delivery. Post-term birth (≥ 42 weeks), birth weight and fetal growth were not associated with maternal prenatal emotions.

Conclusions

This study with 14 measurements of maternal emotions during pregnancy show modest effects of prenatal emotions during the third pregnancy trimester, particularly in the weeks close to delivery, on gestational length. From the clinical perspective, the effects were negligible. No associations were detected between prenatal emotions and birth weight.     

Effects of Prenatal Multiple Micronutrient Supplementation on Fetal Growth Factors: A Cluster-Randomized,Controlled Trial in Rural Bangladesh

Prenatal multiple micronutrient (MM) supplementation improves birth weight through increased fetal growth and gestational age, but whether maternal or fetal growth factors are involved is unclear. Our objective was to examine the effect of prenatal MM supplementation on intrauterine growth factors and the associations between growth factors and birth outcomes in a rural setting in Bangladesh. In a double-blind, cluster-randomized, controlled trial of MM vs. iron and folic acid (IFA) supplementation, we measured placental growth hormone (PGH) at 10 weeks and PGH and human placental lactogen (hPL) at 32 weeks gestation in maternal plasma (n = 396) and insulin, insulin-like growth factor-1 (IGF-1), and IGF binding protein-1 (IGFBP-1) in cord plasma (n = 325). Birth size and gestational age were also assessed. Early pregnancy mean (SD) BMI was 19.5 (2.4) kg/m² and birth weight was 2.68 (0.41) kg. There was no effect of MM on concentrations of maternal hPL or PGH, or cord insulin, IGF-1, or IGFBP-1. However, among pregnancies of female offspring, hPL concentration was higher by 1.1 mg/L in the third trimester (95% CI: 0.2, 2.0 mg/L; p = 0.09 for interaction); and among women with height <145 cm, insulin was higher by 59% (95% CI: 3, 115%; p = 0.05 for interaction) in the MM vs. IFA group. Maternal hPL and cord blood insulin and IGF-1 were positively, and IGFBP-1 was negatively, associated with birth weight z score and other measures of birth size (all p<0.05). IGF-1 was inversely associated with gestational age (p<0.05), but other growth factors were not associated with gestational age or preterm birth. Prenatal MM supplementation had no overall impact on intrauterine growth factors. MM supplementation altered some growth factors differentially by maternal early pregnancy nutritional status and sex of the offspring, but this should be examined in other studies.

Trial Registration

ClinicalTrials.gov NCT00860470