To estimate the effect of partner change on risks of pre-eclampsia and giving birth to a small for gestational age infant.
Prospective population study.
Women with their first and second successive singleton births in Sweden between 1990 and 2006 without pregestational diabetes and/or hypertension (n=446 459).
Preterm (<37 weeks) and term (≥37 weeks) pre-eclampsia, and giving birth to a small for gestational age (SGA) infant. Risks were adjusted for interpregnancy interval, maternal age, body mass index, height and smoking habits in second pregnancy, years of involuntary childlessness before second pregnancy, mother's country of birth, years of formal education and year of birth. Further, when we calculated risks of SGA we restricted the study population to women with non-pre-eclamptic pregnancies.
In women who had a preterm pre-eclampsia in first pregnancy, partner change was associated with a strong protective effect for preterm pre-eclampsia recurrence (OR 0.24; 95% CI 0.07 to 0.88). Similarly, partner change was also associated with a protective effect of recurrence of SGA birth (OR 0.75; 95% CI 0.67 to 0.84). In contrast, among women without SGA in first birth, partner change was associated with an increased risk of SGA in second pregnancy. Risks of term pre-eclampsia were not affected by partner change.
There is a paternal effect on risks of preterm pre-eclampsia and giving birth to an SGA infant.
Gestational diabetes is a risk factor for large-for-gestational-age (LGA) newborns, but many LGA babies are born to mothers with normal glucose tolerance. We aimed to clarify the association of maternal glycemia across the whole distribution with birth weight and risk of LGA births in mothers with normal glucose tolerance.
RESEARCH DESIGN AND METHODS
We undertook a population-based gestational diabetes screening in an urban area of Hungary in 2002–2005. All singleton pregnancies of mothers ≥18 years of age, without known diabetes or gestational diabetes (World Health Organization criteria) and data on a 75-g oral glucose tolerance test at 22–30 weeks of gestation, were included (n = 3,787, 78.9% of the target population). LGA was determined as birth weight greater than the 90th percentile using national sex- and gestational age–specific charts.
Mean ± SD maternal age was 30 ± 4 years, BMI was 22.6 ± 4.0 kg/m2, fasting blood glucose was 4.5 ± 0.5 mmol/l, and postload glucose was 5.5 ± 1.0 mmol/l. The mean birth weight was 3,450 ± 476 g at 39.2 ± 1.2 weeks of gestation. There was a U-shaped association of maternal fasting glucose with birth weight (Pcurve = 0.004) and risk of having an LGA baby (lowest values between 4 and 4.5 mmol/l, Pcurve = 0.0004) with little change after adjustments for clinical characteristics. The association of postload glucose with birth weight (P = 0.03) and the risk of an LGA baby (P = 0.09) was weaker and linear.
Both low and high fasting glucose values at 22–30 weeks of gestation are associated with increased risk of an LGA newborn. We suggest that the excess risk related to low glucose reflects the increased use of nutrients by LGA fetuses that also affects the mothers' fasting glucose.
Adipokines (cytokines produced by adipose tissue) play a major role in the control of body weight and energy distribution. Retinol-binding protein (RBP) 4, only recently recognized as an adipokine, has been proposed to modulate systemic insulin sensitivity. The goal of this study was to determine whether there is an association between maternal plasma RBP4 concentration and the birth of a large-for-gestational-age (LGA) newborn in women with and without gestational diabetes mellitus (GDM).
This cross-sectional study included pregnant women at term in the following groups: 1) normal pregnancy with an appropriate-for-gestational-age (AGA) neonate (n=64); 2) normal pregnancy with an LGA neonate (n=44); 3) GDM with an AGA neonate (n=55); and 4) GDM with an LGA neonate (n=42). Maternal plasma RBP4 concentration was determined by ELISA. Parametric and non-parametric statistics were used for analyses.
1) Patients with GDM, either with AGA or LGA neonates, had a higher median plasma concentration of RBP4 than normal pregnant women who delivered an AGA neonate (p=0.01 and p=0.008, respectively); 2) mothers without GDM but with LGA neonates had a higher median plasma concentration of RBP4 than those with normal pregnancy and AGA newborns (p=0.001); 3) these findings remained significant after adjusting for maternal age, BMI and gestational age at blood sampling.
GDM is characterized by alterations in maternal circulating RBP4 concentrations akin to those of Type 2 DM. Retinol binding protein 4 concentrations in maternal plasma may play a role in accelerated fetal growth in the absence of overt carbohydrate intolerance.
metabolism; pregnancy; appropriate-for-gestational-age (AGA); adipokine; cytokine; adipose tissue; BMI; overweight; obesity; insulin resistance; insulin sensitivity
Intensified management of gestational diabetes mellitus can normalize birth weight. However, it is still unknown whether intrauterine exposure to maternal diabetes is a risk factor for changing hormone levels involved in the development of insulin resistance in these infants. We compared insulin and leptin levels in appropriate for gestational age (AGA) infants of diabetic and non diabetic mothers.
We performed a cross-sectional study in the department of Neonatology of the Hospital of Gynecology-Pediatrics, in Leon, Mexico. We evaluated 182 full term AGA newborns (86 infants of diabetic and 96 of non-diabetic mothers). A venous blood sample was taken from cord blood immediately after the separation of the placenta and glucose, insulin and leptin levels were measured. In all diabetic mothers HbA1c was also evaluated immediately post-partum.
Leptin, insulin and insulin resistance index were significantly higher in infants of diabetic mothers. Leptin levels were positive correlated with insulin, parents‘ body mass index and age in the entire group. In infants of diabetic mothers only insulin levels showed a significantly correlation, whereas in those of non-diabetic mothers only mothers‘ age was significantly correlated with leptin levels.
AGA infants of diabetic mothers showed higher leptin, insulin levels and insulin resistance index than those of non-diabetic mothers.
Diabetic Mother; Insulin; Leptin; Birthweight; Infant
Adipose tissue dysfunction, characterized by dysregulation of adipokines production and/or secretion, has been implicated in the pathophysiology of type-2 diabetes mellitus, a metabolic complication closely related to gestational diabetes mellitus (GDM). Recently, an association between circulating maternal visfatin, a novel adipokine with metabolic and immunoregulatory properties, and impaired glucose metabolism as well as with altered fetal growth, has been proposed. The aims of this study were to determine whether there is an association between maternal plasma visfatin concentration, GDM, and a large-for-gestational-age (LGA) newborn.
This cross-sectional study, included pregnant women at term in the following groups: 1) normal pregnancy and an appropriate-for-gestational-age (AGA) neonate (n=54); 2) normal pregnancy and an LGA newborn (n=47); 3) GDM and an AGA newborn (n=56); 4) GDM and an LGA newborn (n=45). The study population was further stratified by first trimester BMI (<25 vs. ≥25 kg/m2). Maternal plasma visfatin concentration was determined by ELISA. Parametric and non-parametric statistics were used for analysis.
1) Among women who delivered an AGA neonate, the median maternal plasma concentration of visfatin was higher in patients with GDM than in those with a normal pregnancy; 2) Among women with a normal pregnancy, those who delivered an LGA neonate had a higher median maternal plasma visfatin concentration than those who delivered an AGA neonate; 3) among patients with normal BMI, there were no significant differences in the median maternal plasma visfatin concentration between the four study groups; and 4) maternal GDM, as well as delivery of an LGA neonate were independently associated with a higher maternal plasma visfatin concentrations.
The linkage between increased maternal circulating visfatin and the presence of GDM or delivery of an LGA neonate supports the hypothesis that perturbation of adipokines homeostasis may play a role in the pathophysiology of GDM or excess fetal growth.
Visfatin; gestational diabetes mellitus (GDM); large-for-gestational-age (LGA); appropriate-for-gestational-age (AGA); pre-B cell colony-enhancing factor (PBEF); adipokine; adipose tissue
► A trend for lower level of all placental hGH/CSH transcripts in preeclampsia. ► Reduced GH2-2/CSH1-2 transcripts retaining intron 4 only in preeclampsia without SGA. ► Increased level of placental GH2 mRNA in gestational diabetes with LGA newborns. ► hGH/CSH genes exhibit pleiotropic effects on fetal growth and maternal metabolism.
The human GH/CSH cluster consisting of one pituitary-expressed (GH1) and four placenta-expressed loci has been implicated in maternal metabolic adaptation to pregnancy, regulation of intrauterine and postnatal growth. We investigated how the mRNA expression profile of placental GH2, CSH1 and CSH2 genes and their alternative transcripts correlates with maternal pre-eclampsia (PE) and/or gestational diabetes mellitus (GD). The expression of studied genes in PE placentas (n = 17) compared to controls (n = 17) exhibited a trend for reduced transcript levels. The alternative transcripts retaining intron 4, GH2-2 and CSH1-2 showed significantly reduced expression in PE cases without growth restriction (P = 0.007, P = 0.008, respectively). In maternal GD (n = 23), a tendency of differential expression was detected only for the GH2 gene and in pregnancies with large-for-gestational-age newborns. Our results, together with those reported by others, are consistent with a pleiotropic effect of placental hGH/CSH genes at the maternal-fetal interface relating to the regulation of fetal growth and the risk of affected maternal metabolism.
hGH/CSH genes; Placental expression; Pre-eclampsia; Gestational diabetes mellitus; Alternative mRNA transcripts; Fetal growth
STUDY OBJECTIVE: To assess the relation between leisure time physical activity (LTPA) during the first 20 weeks of pregnancy and the risk of developing pre-eclampsia and gestational hypertension. DESIGN: Case-control study carried out over a 28 month period with retrospective data collection. SETTING: Six hospitals in Quebec City and four hospitals in Montreal. PARTICIPANTS: 172 women with pre-eclampsia, 254 with gestational diabetes, 505 controls. All were primiparous, with no history of high blood pressure before pregnancy (unless due to oral contraceptive use), or during the first 20 weeks of gestation. Cases were defined using recognised criteria, and 97% of those eligible agreed to be interviewed. Controls delivered in same hospital immediately after cases and had no more than one reading of elevated blood pressure during pregnancy; 96% of those eligible agreed to be interviewed. MEASUREMENTS AND MAIN RESULTS: Participants were interviewed in hospital a few days after delivery using a questionnaire. Information was collected on type, frequency and average duration of any LTPA performed regularly during the first 20 weeks of pregnancy, together with medical, obstetric and sociodemographic details. It was found that women who performed regular LTPA had a reduced risk of pre-eclampsia (adjusted RR 0.67, 95% CI 0.46-0.96) and gestational hypertension (aRR 0.75, 95% CI 0.54-1.05), and the relative risks decreased as the average time spent in LTPA increased (aRR for pre-eclampsia among women with low, moderate and high energy expenditure: 1.00, 0.77 and 0.57, p = 0.01). The same trend was present for gestational hypertension (1.00, 0.80 and 0.71, respectively, p = 0.08). CONCLUSIONS: Leisure time physical activity during the first half of pregnancy is likely to reduce the risk of pre-eclampsia and gestational hypertension.
The objective of this study was to assess the status of oxidative stress in term small for gestational age (SGA) newborn infants born to undernourished mothers by estimating levels of erythrocyte superoxide dismutase (SOD), catalase, reduced glutathione, and serum malondialdehyde (MDA) in cord blood and comparing them to healthy appropriate for gestational age (AGA) controls. This was done in a case control design at a tertiary level teaching hospital.
We included 20 singleton healthy SGA newborn infants born between 38–40 weeks to undernourished mothers with a) post-pregnancy weight < 50 kg or height < 145 cm AND b) hemoglobin < 8.0 g/dL or serum albumin < 2.5 g/dL. An equal number of age and sex matched AGA newborn infants born to healthy mothers served as Controls. Mothers with other risk factors and newborns with complications during delivery or immediate newborn period were excluded. MDA, SOD, catalase and reduced glutathione were measured in the cord blood of all neonates and compared between the groups (unpaired t test); levels were also correlated to maternal weight, height, hemoglobin, and albumin by both univariate (pearsonian correlation) and multivariate (multiple regression) analysis.
The activity of MDA was increased (5.33 ± 0.72 vs 2.55 ± 0.22 nmol/mL; P < 0.0001) while levels of superoxide dismutase (493.6 ± 54.9 vs. 786.8 ± 79.1 U/g Hb; P < 0.0001), catalase (1.48 ± 0.24 vs. 2.31 ± 0.20 U/g Hb; P < 0.0001) and reduced glutathione (2.84 ± 0.37 vs 6.42 ± 0.23 Umol/g Hb, P < 0.0001) were decreased in term SGA born to undernourished mothers as compared to term AGA born to healthy mothers. On univariate analysis, all the markers of oxidative stress correlated significantly with maternal parameters (P < 0.005). On multivariate analysis, maternal albumin and hemoglobin accounted for maximum correlation with the markers of oxidative stress.
Intrauterine malnutrition is associated with significant oxidative stress in small for gestational age neonates born at term to malnourished mothers.
AIM—To study the
relation between fetal growth and markers of collagen metabolism and
insulin-like growth factor binding protein-1 (IGFBP-1) in term infants.
plasma was obtained from 67 term infants of gestational age 37.1-41.7
weeks (39 appropriate for gestational age (AGA), 11 large for
gestational age (LGA; relative birth weight ⩾ 2.0 SD), and 17 small
for gestational age (SGA; relative birth weight ⩽ −2.0 SD)) for
analysis of markers of metabolism of collagen type I (PICP and ICTP)
and III (PIIINP) and of IGFBP-1.
correlations existed between gestational age and PICP
(r = −0.294, p = 0.0158), ICTP
(r = −0.338, p = 0.0052), and PIIINP
(r = −0.432, p = 0.0003). These
correlations were also found in SGA infants (all p < 0.05). IGFBP-1
showed negative correlations with birth weight and relative birth
weight (r = −0.644, p = 0.0001, and
r = −0.693, p = 0.0001 respectively)
but not with gestational age (p>0.05).
term fetus, collagen metabolism is primarily dependent on maturity and
not on intrauterine growth status, whereas IGFBP-1 reflects
intrauterine growth independently of maturity.
AIMS—To investigate the effect of
maternal diabetes on leptin in term newborns and to determine whether
leptin correlates with insulin and its associated biochemical
parameters in support of the hypothesis that a functional
"adipoinsular axis" might exist at this stage of development.
METHODS—A total of 116 term
newborns were prospectively enrolled and categorised into three groups:
44 were infants of non-diabetic mothers (control group C); 41 were
infants born to mothers with gestational diabetes on dietary treatment
(group D); and 31 were infants born to mothers with gestational or
pregestational diabetes on insulin treatment (group I).
RESULTS—No significant difference
in serum leptin was observed between the three groups; the results of
the study population were therefore pooled and analysed. Serum leptin
correlated significantly with serum insulin, insulin:glucose ratio,
birth weight, body length, body mass index, placenta weight, and
maternal HbA1c. Female infants had significantly higher
serum leptin than male infants. All parameters except placenta weight
and body length remained significantly associated with serum leptin
when multivariate stepwise regression analysis was applied. Subgroup
analysis revealed a significant correlation between serum leptin and
cortisol in group D.
CONCLUSIONS—There was no
significant difference in serum leptin between infants born to diabetic
and non-diabetic mothers, though infants born to mothers requiring
insulin treatment had the highest median serum leptin concentrations.
The significant association between serum leptin and insulin or
insulin:glucose ratio supports the hypothesis that a functional
adipoinsular axis might exist in term newborns. Furthermore, the
significant correlation between maternal HbA1c and
circulating leptin of the studied infants suggests that the clinical
control of maternal diabetes could affect the regulation of serum
leptin in these infants.
An active "adipoinsular axis" is likely to exist in
term newborns. The clinical control of maternal diabetes may affect the
regulation of serum leptin and possibly may also influence the growth
of the fetus in utero
The Canadian guidelines recommend blood glucose (BG) screening starting at 2 h of age in asymptomatic ‘at-risk’ babies (including small-for-gestational-age [SGA] and large-for-gestational-age [LGA] infants), with intervention cut-offs of 1.8 mmol/L and 2.6 mmol/L. The present study reviews and audits this practice in full-term newborn populations.
A literature review meta-analyzed BG values in appropriate-for-gestational age (AGA) term newborns to establish normal 1 h, 2 h and 3 h values. A clinical review audited screening of ‘at-risk’ SGA and LGA term newborns, evaluating both clinical burden and validity.
The review included six studies, although none clearly defined the plasma glucose standard. The pooled mean (plasma) BG level in AGA babies 2 h of age was 3.35 mmol/L (SD=0.77), significantly higher than 1 h levels (3.01 mmol/L, SD=0.96). In the audit, 78 SGA and 142 LGA babies each had an average of 6.0 and 4.7 BG tests, respectively. The mean 2 h BG levels for SGA (3.42 mmol/L, SD=1.02) and LGA (3.31 mmol/L, SD=0.66) babies did not differ significantly from the AGA pooled mean. Receiver operating characteristic curves showed that 2 h BG levels in LGA and SGA babies predicted later hypoglycemia (defined as a BG level lower than 2.6 mmol/L), but sensitivities and specificities were poor.
Published 2 h BG levels for AGA babies are higher than 1 h values and are similar to audited 2 h levels in SGA and LGA babies. Clinically, 2 h levels are predictive of later hypoglycemia but may require repeat BG testing. Audit is an important tool to validate national guidelines, to minimize their burden and to maximize their utility.
Blood glucose; Hypoglycemia; Large for gestational age; Neonatal; Normal values; Plasma glucose; Small for gestational age
Isolated gestational proteinuria may be part of the pre-eclampsia disease spectrum. Confirmation of its association with established pre-eclampsia risk factors and higher blood pressure in uncomplicated pregnancies would support this concept.
Data from 11,651 women from the Avon Longitudinal Study of Parents and Children who had a term live birth but did not have pre-existing hypertension or diabetes or develop gestational diabetes or preeclampsia were used. Proteinuria was assessed repeatedly (median 12 measurements per woman) by dipstick and latent class analysis was used to identify subgroups of the population with different patterns of proteinuria in pregnancy.
Higher maternal pre-pregnancy body mass index (BMI), younger age, nulliparity and twin pregnancy were independently associated with increased odds of any proteinuria in pregnancy. Women who experienced proteinuria showed five patterns: proteinuria in early pregnancy only (≤20 weeks gestation), and onset at 21–28 weeks, 29–32 weeks, 33–36 weeks and ≥37 weeks gestation. There were higher odds of proteinuria onset after 33 weeks in obese women and after 37 weeks in nulliparous women compared with normal weight and multiparous women respectively. Smoking in pregnancy was weakly negatively associated with odds of proteinuria onset after 37 weeks. Twin pregnancies had higher odds of proteinuria onset from 29 weeks. In women with proteinuria onset after 33 weeks blood pressure was higher in early pregnancy and at the end of pregnancy.
Established pre-eclampsia risk factors were related to proteinuria occurrence in late gestation in healthy term pregnancies, supporting the hypothesis that isolated gestational proteinuria may represent an early manifestation of pre-eclampsia.
Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.
Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.
This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.
NTR1792 Clinical trial registration: http://www.trialregister.nl
To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers.
RESEARCH DESIGN AND METHODS
At 6–7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T).
LGA children had higher levels of leptin (P < 0.01), fasting insulin (P < 0.01), and HOMA-IR (P < 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P < 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016).
Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.
The term small for gestational age (SGA) refers to infants whose birth weights and/or lengths are at least two standard deviation (SD) units less than the mean for gestational age. This condition affects approximately 3%–10% of newborns. Causes for SGA birth include environmental factors, placental factors such as abnormal uteroplacental blood flow, and inherited genetic mutations. In the past two decades, an enhanced understanding of genetics has identified several potential causes for SGA. These include mutations that affect the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis, including mutations in the IGF-1 gene and acid-labile subunit (ALS) deficiency. In addition, select polymorphisms observed in patients with SGA include those involved in genes associated with obesity, type 2 diabetes, hypertension, ischemic heart disease and deletion of exon 3 growth hormone receptor (d3-GHR) polymorphism. Uniparental disomy (UPD) and imprinting effects may also underlie some of the phenotypes observed in SGA individuals. The variety of genetic mutations associated with SGA births helps explain the diversity of phenotype characteristics, such as impaired motor or mental development, present in individuals with this disorder. Predicting the effectiveness of recombinant human GH (hGH) therapy for each type of mutation remains challenging. Factors affecting response to hGH therapy include the dose and method of hGH administration as well as the age of initiation of hGH therapy. This article reviews the results of these studies and summarizes the success of hGH therapy in treating this difficult and genetically heterogenous disorder.
Growth hormone; Small for gestational age; Insulin-like growth factor; Acid-labile subunit deficiency; Uniparental disomy
Aims—To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system.
Methods—Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers.
Results—In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns.
Conclusion—Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases.
Key Words: apolipoproteins • lipids • lipoproteins • lecithin:cholesterol acyltransferase • fetal macrosomia • maternal type 1 diabetes
There are differences in the literature regarding outcomes of premature small-for-gestational-age (SGA) and appropriate-for gestational-age (AGA) infants, possibly due to failure to take into account gestational age at birth.
To compare mortality and respiratory morbidity of SGA and AGA premature newborn infants.
A retrospective study was done of the 2,487 infants born without congenital anomalies at ≤36 weeks of gestation and admitted to the neonatal intensive care unit (NICU) at John Dempsey Hospital, between Jan. 1992 and Dec. 1999. Recent (1994–96) U.S. birth weight percentiles for gestational age (GA), race and gender were used to classify neonates as SGA (<10th percentile for GA) or AGA (10th–90th percentile for GA). Using multivariate logistic regression and survival analyses to control for GA, SGA and AGA infants were compared for mortality and respiratory morbidity.
Controlling for GA, premature SGA infants were at a higher risk for mortality (Odds ratio 3.1, P = 0.001) and at lower risk of respiratory distress syndrome (OR = 0.71, p = 0.02) than AGA infants. However multivariate logistic regression modeling found that the odds of having respiratory distress syndrome (RDS) varied between SGA and AGA infants by GA. There was no change in RDS risk in SGA infants at GA ≤ 32 wk (OR = 1.27, 95% CI 0.32 – 1.98) but significantly decreased risk for RDS at GA > 32 wk (OR = 0.41, 95% CI 0.27 – 0.63; p < 0.01). After controlling for GA, SGA infants were observed to be at a significantly higher risk for developing chronic lung disease as compared to AGA infants (OR = 2.2, 95% CI = 1.2 – 3.9, P = 0.01). There was no significant difference between SGA and AGA infants in total days on ventilator. Among infants who survived, mean length of hospital stay was significantly higher in SGA infants born between 26–36 wks GA than AGA infants.
Premature SGA infants have significantly higher mortality, significantly higher risk of developing chronic lung disease and longer hospital stay as compared to premature AGA infants. Even the reduced risk of RDS in infants born at ≥32 wk GA, (conferred possibly by intra-uterine stress leading to accelerated lung maturation) appears to be of transient effect and is counterbalanced by adverse effects of poor intrauterine growth on long term pulmonary outcomes such as chronic lung disease.
To investigate the association between weekly weight gain, during the second and third trimesters, classified according to the 2009 Institute of Medicine (IOM/NRC) recommendations, and maternal and fetal outcomes.
Gestational weight gain was evaluated in 2,244 pregnant women of the Brazilian Study of Gestational Diabetes (Estudo Brasileiro do Diabetes Gestacional – EBDG). Outcomes were cesarean delivery, preterm birth and small or large for gestational age birth (SGA, LGA). Associations between inadequate weight gain and outcomes were estimated using robust Poisson regression adjusting for pre-pregnancy body mass index, trimester-specific weight gain, age, height, skin color, parity, education, smoking, alcohol consumption, gestational diabetes and hypertensive disorders in pregnancy.
In fully adjusted models, in the second trimester, insufficient weight gain was associated with SGA (relative risk [RR] 1.72, 95% confidence interval [CI] 1.26–2.33), and excessive weight gain with LGA (RR 1.64, 95% CI 1.16–2.31); in third trimester, excessive weight gain with preterm birth (RR 1.70, 95% CI 1.08–2.70) and cesarean delivery (RR 1.21, 95% CI 1.03–1.44). Women with less than recommended gestational weight gain in the 2nd trimester had a lesser risk of cesarean deliveries (RR 0.82, 95% CI 0.71–0.96) than women with adequate gestational weight gain in this trimester.
Though insufficient weight gain in the 3rd trimester was not associated with adverse outcomes, other deviations from recommended weight gain during second and third trimester were associated with adverse pregnancy outcomes. These findings support, in part, the 2009 IOM/NRC recommendations for nutritional monitoring during pregnancy.
Maternal minority status is a risk factor for iron deficiency in infancy and pregnancy. Because language and cultural differences may limit research participation, a prospective study examining iron deficiency included maternal minority status as an inclusionary criterion. Cognizant of potential barriers to recruitment, goals were to quantify eligible Latina enrollees and refusals, examine participation barriers, and devise possible solutions.
Mothers and their full-term newborns were eligible if the women were anemic, diabetic during pregnancy, of minority and/or lower socioeconomic status, and/or delivered an infant outside the average weight range for gestational age. Self-reported ethnicity and reasons for participation refusal were documented.
During the first 18 months, 255 mothers and their infants were enrolled. Based on inclusionary criteria and the percentage of minority women admitted to the birthing center in a year, we anticipated 25% minority enrollees, with 16.3% Latina. Although 27% minority enrollment was obtained, only 8% were Latina (P < 0.01). System barriers, researcher perception barriers, and participant perception barriers were encountered. Over the next 8 months, addressing these recruitment barriers improved Latina enrollment.
Enrollment barriers are significant hurdles to overcome, but with increased understanding and effort, more successful inclusion of Latina families can be achieved.
The influence of multiple maternal and pregnancy characteristics on offspring cardiometabolic traits at birth is not well understood and was evaluated in this study.
Methods and Findings
The Family Atherosclerosis Monitoring In earLY life (FAMILY) Study prospectively evaluated 11 cardiometabolic traits in 901 babies born to 857 mothers. The influence of maternal age, health (pre-pregnancy weight, blood pressure, glycemic status, lipids), health behaviors (diet, activity, smoking) and pregnancy characteristics (gestational age at birth, gestational weight gain and placental-fetal ratio) were examined. Greater gestational age influenced multiple newborn cardiometabolic traits including cord blood lipids, glucose and insulin, body fat and blood pressure. In a subset of 442 singleton mother/infant pairs, principal component analysis grouped 11 newborn cardiometabolic traits into 5 components (anthropometry/insulin, 2 lipid components, blood pressure and glycemia), accounting for 74% of the variance of the 11 outcome variables. Determinants of these components, corrected for sex and gestational age, were examined. Baby anthropometry/insulin was independently predicted by higher maternal pre-pregnancy weight (standardized estimate 0.30) and gestational weight gain (0.30; both p<0.0001) and was inversely related to smoking during pregnancy (−0.144; p = 0.01) and maternal polyunsaturated to saturated fat intake (−0.135;p = 0.01). Component 2 (HDL-C/Apo Apolipoprotein1) was inversely associated with maternal age. Component 3 (blood pressure) was not clustered with any other newborn cardiometabolic trait and no associations with maternal pregnancy characteristics were identified. Component 4 (triglycerides) was positively associated with maternal hypertension and triglycerides, and inversely associated with maternal HDL and age. Component 5 (glycemia) was inversely associated with placental/fetal ratio (−0.141; p = 0.005). LDL-C was a bridging variable between the lipid factors and glycemia.
Maternal health, health behaviours and placenta to fetal weight ratio are associated with newborn cardiometabolic traits over and above gestational age. Future investigations are needed to determine if these factors remain important determinants of cardiometabolic health throughout childhood.
To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (≥8.0%) glycemic control, respectively.
Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values ≥6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values ≥7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.
Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.
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 (SGA) and 870 controls (appropriate size for gestational age (AGA)). Only term (37+ completed weeks of gestation) infants were included. Retrospective food frequency questionnaires were completed at birth on the diet at the time of conception and in the last month of pregnancy.
Results: At the time of conception, mothers of AGA infants ate significantly more servings of carbohydrate rich food and fruit, and were more likely to have taken folate and vitamin supplements than mothers of SGA infants. There was some evidence that mothers of AGA infants also ate more servings of dairy products, meat, and fish (0.05 < p < 0.1). However, after adjustment for maternal ethnicity, smoking, height, weight, hypertension, and occupation, fish intake (p = 0.04), carbohydrate-rich foods (p = 0.04), and folate supplementation (p = 0.02) were associated with a reduced risk of SGA. In the last month of pregnancy, only iron supplementation was associated with a reduced risk of SGA (p = 0.05) after adjustment for potential confounders.
Conclusions: This study suggests that small variations in maternal diets within the normal range during pregnancy in developed countries are associated with differences in birth weight.
In adults, the TCF7L2 rs7903146 T allele, commonly associated with type 2 diabetes (T2D), has been also associated with a lower body mass index (BMI) in T2D individuals and with a smaller waist circumference in subjects with impaired glucose tolerance.
The present association study aimed at analyzing the contribution of the rs7903146 SNP to smallness for gestational age (SGA) and metabolic profiles in subjects with SGA or appropriate for gestational age birth weight (AGA). Two groups of French Caucasian subjects were selected on birth data: SGA (birth weight < 10th percentile; n = 764), and AGA (25th < birth weight < 75th percentile; n = 627). Family-based association tests were also performed in 3,012 subjects from 628 SGA and AGA pedigrees.
The rs7903146 genotypic distributions between AGA (30.7%) and SGA (29.0%) were not statistically different (allelic OR = 0.92 [0.78–1.09], p = 0.34). Family association-based studies did not show a distortion of T allele transmission in SGA subjects (p = 0.52). No significant effect of the T allele was detected on any of the metabolic parameters in the SGA group. However, in the AGA group, trends towards a lower insulin secretion (p = 0.03) and a higher fasting glycaemia (p = 0.002) were detected in carriers of the T allele.
The TCF7L2 rs7903146 variant neither increases the risk for SGA nor modulates birth weight and young adulthood glucose homeostasis in French Caucasian subjects born with SGA.
To evaluate the effects of early-onset and late-onset pre-eclampsia on fetal growth.
Longitudinal prospective analytical survey
Obstetrics unit of Department of Obstetrics and Gynaecology in Korle Bu Teaching Hospital.
Subjects and Methods
11,784 nulliparous women carrying singleton pregnancy were prospectively followed up based on a schedule of antenatal care from 14–16 weeks gestation till delivery. Exclusion criteria included obesity (BMI>30.0), underweight (BMI<18.5), chronic hypertension, diabetes mellitus, chronic renal disease, connective tissue diseases, hyperthyroidism, hypothyroidism, cardiac disease, HIV/AIDS, anaemia (Hb<10.0 g/dL), malaria during the index pregnancy, alcohol abuse and cigarette smoking. The selected women were observed for onset of pre-eclampsia, timing of delivery, and baby's birth weight and crown-heel length for each baby were entered into a register. The ponderal index of each baby at birth was also computed.
The incidence of pre-eclampsia in the 11,784 women was 7.03%. The babies delivered by mothers who had early-onset (<37 weeks gestation) pre-elampsia, were of significantly lower birth weights (p=0.003 to p=0.02) and ponderal indices (p=0.002 to p=0.02) at all gestational ages of delivery compared with babies of mothers who did not have pre-eclampsia. However, in late-onset (≥37 weeks) pre-eclampsia, the birth weights and ponderal indice at all gestational ages were comparable to non-pre-eclamptics.
These results support the hypothesis that pre-eclampsia is an aetiologically heterogenous disorder that occurs in at least two subsets: a late-onset pre-eclampsia with normal fetal growth denoting normal placental function and an early-onset type with fetal growth restriction implying placental dysfunction.
Pre-eclampsia: early-onset; late-onset; birth weight; ponderal index
Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR) and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (<32 weeks) and with a birth weight too low for their gestational age (less than −1SDS; SGA) with 75 individuals born preterm but with a birth weight appropriate for their gestational age (greater than −1SDS) and a normal postnatal growth (greater than −1SDS at three months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (p = 3.3 × 10−13) and head circumference at birth (p = 4.1 × 10−13). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5, 47.5, 79.4 and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non-epigenetic mechanisms that may lead to similar later health outcomes.
SGA; DOHAD; IUGR; DNA methylation; famine; IGF2; LEP; INS; GNASAS