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Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.
Very preterm infants experience poor postnatal growth relative to intra-uterine growth rates but have increased percentage body fat (%fat). The aim of the present study was to identify nutritional and other clinical predictors of infant %fat, fat mass (FM) (g) and lean mass (LM) (g) in very preterm infants during their hospital stay. Daily intakes of protein, carbohydrate, lipids and energy were recorded from birth to 34 weeks postmenstrual age (PMA) in fifty infants born <32 weeks. Clinical illness variables and anthropometric data were also collected. Body composition was assessed at 34–37 weeks PMA using the PEA POD Infant Body Composition System. Multiple regression analysis was used to identify independent predictors of body composition (%fat, FM or LM). Birth weight, birth weight z-score and PMA were strong positive predictors of infant LM. After adjustment for these factors, the strongest nutrient predictors of LM were protein:carbohydrate ratios (102–318 g LM/0·1 increase in ratio, P = 0·006–0·015). Postnatal age (PNA) and PMA were the strongest predictors of infant FM or %fat. When PNA and PMA were accounted for a higher intake of energy (–1·41 to –1·61 g FM/kJ per kg per d, P = 0·001–0·012), protein (–75·5 to –81·0 g FM/g per kg per d, P = 0·019–0·038) and carbohydrate (–27·2 to –30·0 g FM/g per kg per d, P = 0·012–0·019) were associated with a lower FM at 34–37 weeks PMA. Higher intakes of energy, protein and carbohydrate may reduce fat accumulation in very preterm infants until at least 34–37 weeks PMA.
We investigated whether children born preterm are at risk for language delay using a sibling-control design in the Norwegian Mother and Child Cohort Study (MoBa), conducted by the Norwegian Institute of Public Health. Participants included 26,769 siblings born between gestational weeks 23 and 42. Language delay was assessed when the children were 1.5, 3, and 5 years old. To adjust for familial risk factors, comparisons were conducted between preterm and full-term siblings. Pregnancy-specific risk factors were controlled for by means of observed variables. Findings showed that preterm children born before week 37 had increased risk for language delays at 1.5 years. At 3 and 5 years, only children born before week 34 had increased risk for language delay. Children born weeks 29–33 and before week 29 had increased risk for language delay at 1.5 years (RR = 4.51, 95% CI [3.45, 5.88]; RR = 10.32, 95% CI [6.7, 15.80]), 3 years (RR = 1.50, 95% CI [1.02, 2.21]; RR = 2.78, 95% CI [1.09, 7.07]), and 5 years (RR = 1.63, 95% CI [1.06, 2.51]; RR = 2.98, 95% CI [0.87, 10.26]), respectively. In conclusion, children born preterm are at risk for language delays, with familial confounders only explaining a moderate share of the association. This suggests a cause-effect relationship between early preterm birth and risk for language delay in preschool children.
The first positive genome-wide association study on gestational length and preterm delivery showed the involvement of an Se metabolism gene. In the present study, we examine the association between maternal intake of Se and Se status with gestational length and preterm delivery in 72 025 women with singleton live births from the population-based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitative FFQ answered in pregnancy week 22 was used to estimate Se intake during the first half of pregnancy. Associations were analysed with adjusted linear and Cox regressions. Se status was assessed in whole blood collected in gestational week 17 (n 2637). Median dietary Se intake was 53 (interquartile range (IQR) 44–62) µg/d, supplements provided additionally 50 (IQR 30–75) µg/d for supplement users (n 23 409). Maternal dietary Se intake was significantly associated with prolonged gestational length (β per sd = 0·25, 95 % CI, 0·07, 0·43) and decreased risk of preterm delivery (n 3618, hazard ratio per sd = 0·92, 95 % CI, 0·87, 0·98). Neither Se intake from supplements nor maternal blood Se status was associated with gestational length or preterm delivery. Hence, the present study showed that maternal dietary Se intake but not intake of Se-containing supplements, during the first half of pregnancy was significantly associated with decreased risk of preterm delivery. Further investigations, preferably in the form of a large randomised controlled trial, are needed to elucidate the impact of Se on pregnancy duration.
We examined full-term and preterm infants’ perception of frequent and infrequent phonotactic pairings involving sibilants and liquids. Infants were tested on their preference for syllables with onsets involving /s/ or /ʃ/ followed by /l/ or /r/ using the Headturn Preference Procedure. Full-term infants preferred the frequent to the infrequent phonotactic pairings at 9 months, but not at either younger or older ages. Evidence was inconclusive regarding a possible difference between full-term and preterm samples; however, limitations on the preterm sample size limited our power to detect differences. Preference for the frequent pairing was not related to later vocabulary development.
There is a paucity of functional data on mid-to-late preterm infants between 30+0 and 34+6 weeks gestation. We aimed to characterise transitional cardiopulmonary and haemodynamic changes during the first 48 hours in asymptomatic mid-to-late preterm infants.
Forty-five healthy preterm newborns (mean ± standard deviation) gestation of 32.7 ± 1.2 weeks) underwent echocardiography on Days 1 and 2. Ventricular mechanics were assessed by speckle tracking-derived deformation, rotational mechanics, tissue Doppler imaging, and right ventricle-focused measures (tricuspid annular plane systolic excursion, fractional area change). Continuous haemodynamics were assessed using the NICOM™ system to obtain left ventricular output, stroke volume, heart rate, and total peripheral resistance by non-invasive cardiac output monitoring.
Right ventricular function increased (all measures p < 0.005) with mostly stable left ventricular performance between Day 1 and Day 2. NICOM-derived left ventricular output [mean 34%, 95% confidence interval 21–47%] and stroke volume [29%, 16–42%] increased with no change in heart rate [5%, −2 to 12%]. There was a rise in mean blood pressure [11%, 1–21%], but a decline in total peripheral resistance [−14%, −25 to −3%].
Left ventricular mechanics remained persevered in mid-to-late premature infants, but right ventricular function increased. Non-invasive cardiac output monitoring is feasible in preterm infants with an increase in left ventricular output driven by an improvement in stroke volume during the transitional period.
The neurodevelopmental and trauma theories are two widely cited models of psychosis. A third – the developmental risk factor model (DRFM) – recognises the combined role of neurodevelopmental risks and trauma. Our objective was to test these theories using preterm populations as a natural experiment, given the high prevalence of neurodevelopmental deficits and exposure to trauma.
Two population-based preterm birth cohorts, the Bavarian Longitudinal Study (BLS; N = 399) and EPICure Study (N = 184), were included with term-born controls. Peer victimisation in childhood was assessed by parent and child report and psychotic experiences (PE) were assessed in early adulthood. Different models of psychosis were tested using regression and mediation analyses.
There was support for the trauma and DRFM in the BLS. Peer victimisation increased the risk of PE for preterm and term-born participants equally [odds ratio = 4.87, 95% confidence interval (CI) 1.96–12.08]. There was an indirect effect where preterm children were more likely to be victimised, which subsequently increased risk of PE [β = 1.12 (s.e. = 0.61), 95% CI 0.11–2.48]. The results were replicated in EPICure.
Exposure to trauma which is experienced more often by neurodevelopmental risk children rather than neurodevelopmental risk per se increases the risk of PE. The findings are consistent with the trauma model and DRFM. Interventions focused on reducing trauma may reduce the development of PE.
Both preterm birth and early institutional deprivation are associated with neurodevelopmental impairment—with both shared and distinctive features. To explore shared underlying mechanisms, this study directly compared the effects of these putative risk factors on temperament profiles in six-year-olds: Children born very preterm (<32 weeks gestation) or at very low birthweight (<1500 g) from the Bavarian Longitudinal Study (n = 299); and children who experienced >6 months of deprivation in Romanian institutions from the English and Romanian Adoptees Study (n = 101). The former were compared with 311 healthy term born controls and the latter with 52 nondeprived adoptees. At 6 years, temperament was assessed via parent reports across 5 dimensions: effortful control, activity, shyness, emotionality, and sociability. Very preterm/very low birthweight and postinstitutionalized children showed similarly aberrant profiles in terms of lower effortful control, preterm = −0.50, 95% CI [−0.67, −0.33]; postinstitutionalized = −0.48, 95% CI [−0.82, −0.14], compared with their respective controls. Additionally, postinstitutionalized children showed higher activity, whereas very preterm/very low birthweight children showed lower shyness. Preterm birth and early institutionalization are similarly associated with poorer effortful control, which might contribute to long-term vulnerability. More research is needed to examine temperamental processes as common mediators of negative long-term outcomes following early adversity.
Current evidence indicates that maternal diets before and during pregnancy could influence rates of preterm birth, low birth weight (LBW) and small for gestational age (SGA) births. However, findings have been inconsistent. This review summarised evidence concerning the effects of maternal diets before and during pregnancy on preterm birth, LBW and SGA. Systematic electronic database searches were carried out using PubMed, Embase, Scopus and Cochrane library using the preferred reporting items for systematic reviews and meta-analyses guidelines. The review included forty eligible articles, comprising mostly of prospective cohort studies, with five randomised controlled trials. The dietary patterns during pregnancy associated with a lower risk of preterm birth were commonly characterised by high consumption of vegetables, fruits, whole grains, fish and dairy products. Those associated with a lower risk of SGA also had similar characteristics, including high consumption of vegetables, fruits, legumes, seafood/fish and milk products. Results from a limited number of studies suggested there was a beneficial effect on the risk of preterm birth of pre-pregnancy diet quality characterised by a high intake of fruits and proteins and less intake of added sugars, saturated fats and fast foods. The evidence was mixed for the relationship between maternal dietary patterns during pregnancy and LBW. These findings indicate that better maternal diet quality during pregnancy, characterised by a high intake of vegetables, fruits, whole grains, dairy products and protein diets, may have a synergistic effect on reducing the risk of preterm birth and SGA.
Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22–3.06; aOR2 = 2.05, 95% CI: 1.33–3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30–3.11; aOR2 = 2.51, 95% CI: 1.69–3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03–2.45; aOR2 = 1.99, 95% CI: 1.05–3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.
Better understanding of the variation in macronutrient content of human donor milk (HDM) potentiates targeted nutrition for preterm babies. The present study describes the relationship of maternal age, parity, monthly lactation stage estimate (LSEm), daily volume of milk expressed (Vd), sex, gestation and birth weight z scores with macronutrient content of HDM. Multilevel mother–infant pair ID random intercept models were performed using the predictor variables above on the outcome HDM macronutrient content determined using mid-IR spectroscopy. Mean macronutrient content was also compared by gestational age and small for gestational age (SGA) (z score < –1·28) or appropriate for gestational age (AGA) (z score ≥ –1·28) categories. A total of 2966 samples of donations from 1175 mother–infant pairs to the UK Northwest Human Milk Bank between 2011 and 2017 were analysed. Mean protein, fat, carbohydrate and calculated energy were 0·89 (SD 0·24) g/dl, 2·99 (SD 0·96) g/dl, 7·09 (SD 0·44) g/dl, and 60·37 (SD 8·41) kcal/dl (252·59 (SD 35·19) kJ/dl), respectively. Preterm SGA HDM was significantly higher in protein, fat and energy content than term AGA HDM and significantly lower in carbohydrate content than term AGA HDM after controlling for LSEm, Vd and between-subject effects. Degree of prematurity did not influence macronutrient content. Between-subject effects accounted for more of the variance in macronutrient content than the fixed effects in the model. Despite this, SGA status, as well as prematurity, may be an important determinant of macronutrient content in human milk. As bioavailability of macronutrients from HDM is uncertain, studies evaluating growth and body composition in preterm and SGA babies fed HDM are warranted.
Both inadequate and excessive gestational weight gain (GWG) have been shown to increase the risk of adverse pregnancy outcomes, but the risk profiles of GWG rate are unclear. We aimed to examine the associations between GWG rate in the second/third trimester and a spectrum of pregnancy outcomes. This study consisted of 14 219 Chinese rural nulliparous women who participated in a randomised controlled trial of prenatal micronutrient supplementation during 2006–2009. The outcomes included stillbirth, neonatal and infant death, preterm birth, macrosomia, low birth weight (LBW) and large and small for gestational age (LGA and SGA, respectively). GWG rate was divided into quintiles within each BMI category. Compared with women in the middle quintile, those in the lowest quintile had higher risks of neonatal death (adjusted OR 2·27; 95 % CI 1·03, 5·02), infant death (adjusted OR 1·85; 95 % CI 1·02, 3·37) and early preterm birth (adjusted OR 2·33; 95 % CI 1·13, 4·77), while those in the highest quintile had higher risks of overall preterm birth (adjusted OR 1·28; 95 % CI 1·04, 1·59), late preterm birth (adjusted OR 1·25; 95 % CI 1·00, 1·56), LBW (adjusted OR 1·48; 95 % CI 1·02, 2·15), macrosomia (adjusted OR 1·89; 95 % CI 1·46, 2·45) and LGA (adjusted OR 1·56; 95 % CI 1·31, 1·85). In conclusion, very low and very high GWG rates in the second/third trimester appear to be associated with adverse pregnancy outcomes in Chinese nulliparous women, indicating that an appropriate GWG rate during pregnancy is necessary for neonatal health.
Exclusive breastfeeding is currently recommended until at least 6 months of postnatal age, due to maternal breast milk (BM) unique composition and beneficial properties. In fact, BM modifies itself according to gestational age (GA) at birth, adapting its composition to neonatal requests during lactation. Multiple births represent about 3% of the whole pregnancies; such neonates result more vulnerable than full-term newborns, due to lower GA and birth weight (BW) and the higher incidence of perinatal complications. Although an adequate nutrition is fundamental for twins and other multiples, studies on this topic are lacking. We collected and analyzed BM from mothers of 19 twins and 5 triplets showing GA < 33 weeks and BW < 1500 g, comparing it to a control group of 28 preterm singletons. As a result, at GA ≤ 28 weeks, we observed that protein content is higher in BM for multiples (1.53 vs. 1.29 g per 100 ml), lactose concentration is greater in BM for singletons (6.72 vs. 6.34 g per 100 ml) and GA results the most relevant factor influencing BM protein composition. BM for multiples results higher in proteins and lower in lactose, if compared with singleton’s samples; this could promote and sustain growth and organ development in this vulnerable category. BM from multiples shows a trophic and immunologic role, since these neonates often show lower GA and BW instead of singletons. These findings could help in optimizing nutritional strategies and improving BM individualized fortification.
Little is known about physical constitution outcomes for very preterm infants. Here, we compare z-scores of anthropometric parameters up to 6 years of age in children born with very low birth weight (VLBW) at less than 30 weeks of gestation, with or without intrauterine growth restriction (IUGR).
Participants were divided into four subgroups: male (M), small for gestational age (SGA) (n = 30); M, appropriate for gestational age (AGA) (n = 59); female (F), SGA (n = 24); and F, AGA (n = 61). z-Scores of body weight (BW), body length (BL), and body mass index (BMI) were assessed at birth, 1 year corrected age, 3 years of age, and 6 years of age.
For boys, BW and BMI were significantly lower among SGA children than among AGA children at all assessments, but there was no difference in BL at 3 or 6 years. For girls, BW and BL were significantly lower among SGA children than among AGA children at all assessments, but no difference was detected in BMI after 1.5 years. No significant variation in the z-score of BW or BMI in either SGA group was observed after 1 year. BL z-score in all groups gradually increased until 6 years of age.
IUGR affects BW and BMI in boys and BW and BL in girls during the first 6 years in VLBW children born at less than 30 weeks of gestation. SGA children did not catch up in BW or BMI from 1 to 6 years of age.
Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.
We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.
Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).
Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.
The aim of the study was to investigate any association between extrauterine growth restriction (EUGR) and intestinal flora of <30-week-old preterm infants. A total of 59 preterm infants were assigned to EUGR (n=23) and non-EUGR (n=36) groups. Intestinal bacteria were compared by using high-throughput sequencing of bacterial rRNA. The total abundance of bacteria in 344 genera (7568 v. 13,760; P<0.0001) and 456 species (10,032 v. 18,240; P<0.0001) was significantly decreased in the EUGR group compared with the non-EUGR group. After application of a multivariate logistic model and adjusting for potential confounding factors, as well as false-discovery rate corrections, we found four bacterial genera with higher and one bacterial genus with lower abundance in the EUGR group compared with the control group. In addition, the EUGR group showed significantly increased abundances of six species (Streptococcus parasanguinis, Bacterium RB5FF6, two Klebsiella species and Microbacterium), but decreased frequencies of three species (one Acinetobacter species, Endosymbiont_of_Sphenophorus_lev and one Enterobacter_species) compared with the non-EUGR group. Taken together, there were significant changes in the intestinal microflora of preterm infants with EUGR compared to preterm infants without EUGR.
It has been suggested that the risk of adverse perinatal outcomes in twin pregnancies is exacerbated by concomitant gestational diabetes mellitus (GDM). This study aimed to assess the risk incurred by twin pregnancy and by a diagnosis of GDM, separately, on the development of poor perinatal outcomes. A retrospective cohort study was conducted on all pregnant women at a tertiary center between 2016 and 2017. The impact of GDM and twin pregnancies on perinatal outcomes — birth weight above the 90th centile for gestational age, cesarean delivery, clinical neonatal hypoglycemia, and premature delivery (before 37 weeks’ gestation) — was assessed using univariate and multivariate analyses. Overall, 13,527 women were eligible for the study; 11,915 were uncomplicated singleton pregnancies; 1379 of these had GDM; 194 were twin pregnancies, and 39 of these had GDM. Univariate analyses showed that twin pregnancies were associated with a higher risk of all perinatal outcomes except macrosomia. In the multivariate analyses, twin pregnancy was a much higher predictor of cesarean delivery (OR 8.40, 95% CI [6.25, 11.49], p < .0001) and preterm birth (OR 58.82, 95% CI [31.25, 125], p < .0001) compared to GDM but GDM was a higher predictor of neonatal hypoglycemia (OR 4.87, 95% CI [3.74, 6.29], p < .0001). Twin pregnancy is more strongly associated with all adverse perinatal outcomes except macrosomia. GDM does not increase risk of adverse perinatal outcomes except for neonatal hypoglycemia.
Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity as a mode of respiratory support. We updated a systematic review and meta-analyses examining the efficacy and safety of HHHFNC compared with standard treatments for preterm infants. The primary outcome was the need for reintubation for preterm infants following mechanical ventilation (post-extubation analysis) or need for intubation for preterm infants not previously intubated (analysis of primary respiratory support)
We searched PubMed, MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of HHHFNC versus standard treatments. Meta-analysis was conducted using Review Manager 5.3.
The post-extubation analysis included ten RCTs (n = 1,201), and the analysis of primary respiratory support included ten RCTs (n = 1,676). There were no statistically significant differences for outcomes measuring efficacy, including the primary outcome. There were statistically significant differences favoring HHHFNC versus nasal cannula positive airway pressure (NCPAP) for air leak (post-extubation, risk ratio [RR] 0.29, 95 percent confidence interval [CI] 0.11 to 0.76, I2 = 0) and nasal trauma (post-extubation: 0.35, 95 percent CI 0.27 to 0.46, I2 = 5 percent; primary respiratory support: RR 0.52, 95 percent CI 0.37 to 0.74; I2 = 27 percent). Studies, particularly those of primary respiratory support, included very few preterm infants with gestational age (GA) <28 weeks.
HHHFNC may offer an efficacious and safe alternative to NCPAP for some infants but evidence is lacking for preterm infants with GA ≤28 weeks.
While maternal folate deficiency has been linked to poor pregnancy outcomes such as neural tube defects, anaemia and low birth weight, the relationship between folate and preterm birth (PTB) in the context of the US post-folic acid fortification era is inconclusive. We sought to explore the relationship between maternal folate status and PTB and its subtypes, i.e. spontaneous and medically indicated PTB.
Boston Birth Cohort, a predominantly urban, low-income, race/ethnic minority population at a high risk for PTB.
Mother–infant dyads (n 7675) enrolled in the Boston Birth Cohort. A sub-sample (n 2313) of these dyads had maternal plasma folate samples collected 24–72 h after delivery.
Unadjusted and adjusted logistic regressions revealed an inverse relationship between the frequency of multivitamin supplement intake and PTB. Compared with less frequent use, multivitamin supplement intake 3–5 times/week (adjusted OR (aOR) = 0·78; 95 % CI 0·64, 0·96) or >5 times/week (aOR = 0·77; 95 % CI 0·64, 0·93) throughout pregnancy was associated with reduced risk of PTB. Consistently, higher plasma folate levels (highest v. lowest quartile) were associated with lower risk of PTB (aOR = 0·74; 95 % CI 0·56, 0·97). The above associations were similar among spontaneous and medically indicated PTB.
If confirmed by future studies, our findings raise the possibility that optimizing maternal folate levels across pregnancy may help to reduce the risk of PTB among the most vulnerable US population in the post-folic acid fortification era.
Objectives: The aim of this study was to investigate the effects of infant and toddler head growth on intelligence scores from early childhood to adulthood in very preterm (<32 weeks gestational age; VP) and/or very low birth weight (<1500 g; VLBW) and term born individuals. Methods: 203 VP/VLBW and 198 term comparisons were studied from birth to adulthood as part of the prospective geographically defined Bavarian Longitudinal Study (BLS). Head circumference was assessed at birth; 5, 20 months; and 4 years of age. Intelligence was assessed with standardized tests in childhood (6 and 8 years: K-ABC) and at 26 years (Wechsler Adult Intelligence Scale, WAIS). Structural equation modeling (SEM) was used to model the effect of head growth on IQ. Results: On average, VP/VLBW had lower head circumference at birth (27.61 cm vs. 35.11 cm, mean difference 7.49, 95% confidence interval [7.09–7.90]) and lower adult intelligence scores (88.98 vs. 102.54, mean difference 13.56 [10.59–16.53]) than term born comparison individuals. Head circumference at birth (e.g., total effect β=.48; p<.001 for adult IQ) and head growth in childhood predicted intelligence development from age 6 to 26 years in both VP/VLBW and term born individuals (70% of variance in adult IQ explained by full model). Effects of gestation and birth weight on intelligence were fully mediated by head circumference and growth. Conclusions: This longitudinal investigation from birth to adulthood indicates head growth as a proxy of brain development and intelligence. Repeated early head circumference assessment adds valuable information when screening for long-term neurocognitive risk. (JINS, 2019, 25, 48#x2013;56)