Growth perturbations in a phenotype with rapid fetal growth preceding preterm labor and term birth

The variability in fetal growth rates and gestation duration in humans is not well understood. Of interest are women presenting with an episode of preterm labor and subsequently delivering a term neonate, who is small relative to peers of similar gestational age. To further understand these relationships, fetal growth patterns predating an episode of preterm labor were investigated. Retrospective analysis of fetal biometry assessed by serial ultrasound in a prospectively studied sample of pregnancies in Santiago, Chile, tested the hypothesis that fetal growth patterns among uncomplicated pregnancies (n = 3,706) and those with an episode of preterm labor followed by term delivery (n = 184) were identical across the time intervals 16–22 weeks, 22–28 weeks, and 28–34 weeks in a multilevel mixed‐effects regression. The hypothesis was not supported. Fetal weight growth rate was faster from 16 weeks among pregnancies with an episode of preterm labor (P < 0.05), declined across midgestation (22–28 weeks, P < 0.05), and rebounded between 28 and 34 weeks (P = 0.06). This was associated with perturbations in abdominal circumference growth and proportionately larger biparietal diameter from 22 gestational weeks (P = 0.03), greater femur (P = 0.01), biparietal diameter (P = 0.001) and head circumference (P = 0.02) dimensions relative to abdominal circumference across midgestation (22–28 weeks), followed by proportionately smaller femur diaphyseal length (P = 0.02) and biparietal diameter (P = 0.03) subsequently. A distinctive rapid growth phenotype characterized fetal growth preceding an episode of preterm labor among this sample of term‐delivered neonates. Perturbations in abdominal circumference growth and patterns of proportionality suggest an altered growth strategy pre‐dating the preterm labor episode. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.     

Downward percentile crossing as an indicator of an adverse prenatal environment

Background: Postnatal health sequelae of low birth weight have been attributed to ‘poor fetal growth’ from inferred adverse prenatal environments; risks augmented by infant growth rates. Identifying prenatal growth-restricting events is essential to clarify pathways and mechanisms of fetal growth.

Aim: The specific aim of this investigation was to examine whether an episode of preterm labor may compromise fetal growth.

Subjects and methods: Fetal size at the end of the second trimester and birth were compared among women with uncomplicated pregnancies (n = 3167) and those who experienced an episode of preterm labor (<37 weeks) and subsequently delivered at term (≥37 weeks, n = 147). Fetal weight estimated from ultrasound measures, and changes in weight standard scores across the third trimester investigated significant centile crossing (>0.67 standard deviation score change).

Results: Fetuses delivered at term after an episode of preterm labor were smaller at birth relative to their peers than at the end of the second trimester, and were 47% more likely to experience clinically significant downward centile crossing (p < 0.05) than their peers (OR 1.47, 95% CI 1.04–2.07).

Conclusion: An episode of preterm labor may signal an adverse prenatal environment for term-delivered neonates. Epidemiologically silent events in the natural history of pregnancy are an understudied source of fetal growth compromise as inferred by small birth size among peers.     

Infants thinner at birth exhibit smaller kidneys for their size in late gestation in a sample of fetuses with appropriate growth

Fetal ultrasound measurements were employed to investigate the relationship between weight and ponderal index at birth and kidney size during the second (23 weeks) and third (32 weeks) trimesters of pregnancy in a sample of 25 normally growing fetuses. Kidney volume and kidney volume / fetal weight ratio at 32 weeks are significantly and positively related to both weight and ponderal index at birth, controlling for sex, gestational age at birth, and day of ultrasound measurement. A second‐degree polynomial relationship approximates the predictability of kidney volume fetal weight ratio at 23 weeks to that at 32 weeks, demonstrating shifting growth rates in fetal organ and body growth relationships during midgestation. Sex and parental size are suggested as contributing to these patterns. Females have a surge in renal growth between 23 and 32 weeks to catch up to earlier growing males, and maternal weight significantly predicts incremental growth in kidney volume and the kidney volume / fetal weight ratio at 32 weeks of gestation. The observation that fetuses relatively thin at birth have relatively smaller kidneys for their size in late gestation suggests that the influence of maternal weight on birth outcome may act through organ growth. Am. J. Hum. Biol. 14:398–406, 2002. © 2002 Wiley‐Liss, Inc.     

Pregnancy: Reduced circulating placental protein concentrations during the first trimester are associated with preterm labour and low birth weight

Serum concentrations of human chorionic gonadotrophin (HCG),Schwangerschaftsprotein 1 (SP-1), pregnancy-associated plasmaprotein A (PAPP-A), progesterone and oestradiol were measuredat weekly intervals between the fifth (embryo transfer plus3 weeks) and 13th week of gestation during the first trimesterof pregnancies achieved following in-vitro fertilization (IVF)and embryo transfer in a group of women who delivered before(n = 8) or at term (n = 52). Those women who had a preterm deliveryhad significantly lower concentrations of PAPP-A (weeks 7–13;P = 0.0001–0.028) and SP-1 (weeks 6–8 and 10–12;P = 0.004–0.04). After correction of birth weight forsex and gestational age at delivery, preterm delivery was foundnot to be associated with growth retardation. However, comparisonof the circulating concentrations of the substances analysedin mothers who delivered babies of < 85% of the 50th centileof the normal range of birth weight for a given gestationalage and sex, with those who delivered babies of >85% revealedthat the concentrations of HCG (P = 0.012–0.04 on weeks6–9) and SP-1 (P = 0.003–0.03 on weeks 7, 9–13)were significantly lower in the former group. Weak, inconsistentassociations were found between the circulating concentrationsof HCG, SP-1 and PAPP-A and both corrected birth weight andgestational age at delivery. Thus, both the gestational ageat delivery and low birth weight may be related to impairedplacental development/function during the first trimester.     

Maternal and neonatal interleukin-1 receptor antagonist genotype and pregnancy outcome in a population with a high rate of pre-term birth

Problem We evaluated associations between a length polymorphism in intron 2 of the gene coding for IL‐1ra (gene symbol IL1RN) and pregnancy outcome in a population with a high rate of preterm birth. Method of study Subjects were pregnant women in Maceio, Brazil and their newborns. DNA was tested for IL1RN genotypes and alleles by gene amplification using primer pairs that spanned the polymorphic region. Every subject completed a detailed questionnaire. Results The frequency of allele 2 (IL1RN*2) carriage was elevated in mothers with a spontaneous preterm birth (SPTB) in the current pregnancy (P = 0.02) and also with a prior preterm delivery (P = .01). Both SPTB with intact membranes (P = 0.01) and SPTB preceded by pre‐term pre‐mature rupture of membranes (P = .03) were associated with IL1RN*2 carriage. A previous fetal demise was more than twice as prevalent in mothers positive for two copies of IL1RN*2. Conclusion Maternal carriage of IL1RN*2 increases susceptibility to inflammation‐triggered spontaneous pre‐term birth.     

Sex differences in fetal growth responses to maternal height and weight

Sex differences in fetal growth have been reported, but how this happens remains to be described. It is unknown if fetal growth rates, a reflection of genetic and environmental factors, express sexually dimorphic sensitivity to the mother herself. This analysis investigated homogeneity of male and female growth responses to maternal height and weight. The study sample included 3,495 uncomplicated singleton pregnancies followed longitudinally. Analytic models regressed fetal and neonatal weight on tertiles of maternal height and weight, and modification by sex was investigated (n = 1,814 males, n = 1,681 females) with birth gestational age, maternal parity, and smoking as covariates. Sex modified the effects of maternal height and weight on fetal growth rates and birth weight. Among boys, tallest maternal height influenced fetal weight growth before 18 gestational weeks of age (P = 0.006), and prepregnancy maternal weight and body mass index subsequently had influence (P < 0.001); this was not found among girls. Additionally, interaction terms between sex, maternal height, and maternal weight identified that males were more sensitive to maternal weight among shorter mothers (P = 0.003) and more responsive to maternal height among lighter mothers (P ≤ 0.03), compared to females. Likewise, neonatal birth weight dimorphism varied by maternal phenotype. A male advantage of 60 g occurred among neonates of the shortest and lightest mothers (P = 0.08), compared to 150 and 191 g among short and heavy mothers, and tall and light‐weight mothers, respectively (P = 0.01). Sex differences in response to maternal size are under‐appreciated sources of variation in fetal growth studies and may reflect differential growth strategies. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

Fetal growth restriction and 18‐year growth and nutritional status: Aboriginal birth cohort 1987–2007

The main objective of the work is to compare the growth and nutritional status of Australian Aboriginal term infants born with (n = 81) and without fetal growth restriction (n = 260). A prospective birth cohort study of 341 Aboriginal babies from the Top End of the Northern Territory of Australia was recruited at birth (1987–1990) and re‐examined at a mean age of 18.3 years (2006–2008) for outcome measures of growth and nutrition status. Those with growth restriction at birth were 3 cm shorter (P = 0.0026) and 9 kg lighter (P = 0.0001) with head circumferences 0.95 cm smaller (P = 0.0008) than those without growth restriction. The proportions of growth restricted participants with body mass index <18.5 kg/m² were significantly greater (P = 0.028), and those with BMI > 25 kg/m² and with fat percentage >85th percentile were significantly smaller (P = 0.012 and 0.004, respectively). In this cohort, those Aboriginal babies born smaller and lighter have remained smaller and lighter at 18 years of age. However, the highest risk of later chronic noncommunicable disease has been reported in subjects who were born small and become relatively larger in later life. The continued study of this Aboriginal birth cohort will give us an opportunity to determine if and when in later life the effects of birth weight are modified by environmental nutritional factors. Am. J. Hum. Biol., 2011. © 2010 Wiley‐Liss, Inc.     

Elevated Amniotic Fluid Interleukin-6 Levels During the Early Second Trimester Are Associated With Greater Risk of Subsequent Preterm Delivery

PROBLEM: Subclinical intra-amniotic infection is often associated with preterm delivery and may precede it by several weeks. We tested the hypothesis that Interleukin-6 (IL-6) may be elevated in the midtrimester amniotic fluid of pregnancies destined to deliver preterm. METHODS: A historical cohort study was designed to compare the amniotic fluid (AF) concentrations of IL-6 at 14–20 weeks in a group of women subsequently delivering at ≤ 34 weeks (n = 13) with those of women delivering at term (n = 166). Included were singleton gestations with no evidence of fetal structural or chromosomal abnormalities, or maternal conditions known to be associated with preterm delivery (n = 179). Levels of IL-6 were measured by immunoassay and correlated with demographic and pregnancy outcome information. Statistical analysis included correlation, one-way ANOVA after log-transformation, contingency tables, logistic regression, and receiver operator characteristic (ROC) curve analysis. RESULTS: There was an inverse correlation between AF IL-6 levels at 15–20 weeks and gestational age at delivery (r = ?0.16, P = 0.03). Women delivering at ≤ 34 weeks had significantly higher median AF IL-6 levels (570 pg/ml versus 330 pg/ml, P < 0.0001), rate of African American race (50% versus 12%, P = 0.004), and of infants with birth weights < 10th centile (31% versus 7%, P = 0.02) than women delivering at ≥ 37 weeks. Logistic regression analysis showed that IL-6 was independently associated with PTD at ≤ 34 weeks after controlling for race and birth weight centiles (P = 0.039). CONCLUSIONS: AF IL-6 at 15–20 weeks can identify patients at risk for PTD at ≤ 34 weeks, suggesting that a portion of PTD cases have inciting events that take place during the early second trimester. CAPSULE: Midtrimester amniotic fluid IL-6 concentrations are significantly higher in women subsequently delivering preterm at ≤34 weeks compared with those delivering at term.     

Adenovirus genome in the placenta: association with histological chorioamnionitis and preterm birth

Adenovirus is isolated frequently from the amniotic fluid and has been implicated in severe neonatal infections. A case control study was carried out to examine the association of detection of adenovirus in placentas with preterm birth and histological chorioamnionitis. Placentas from preterm and full term deliveries were collected prospectively. Preterm cases were divided into three subgroups according to the gestational age. PCR was carried out on placental tissues for the detection of adenovirus genome. Placentas were evaluated histologically for the presence of chorioamnionitis. Chi‐square and odds ratios (OR) were used to determine if detection of adenovirus is associated with preterm birth and histological evidence of inflammation. Seventy‐one preterm and 122 full term placentas were studied. Adenovirus genome was detected in 29 (40.8%) of preterm cases and in 25 (20.5%) of the full term controls (OR = 2.6; 95% CI, 1.4–5.1; P = 0.002). Detection of adenovirus in preterm placentas was significantly higher compared to full term particularly in the lower gestational age. Detection of adenovirus in placenta followed the seasonal variation of adenovirus infections. Thirty‐seven preterm and 21 full term placentas were also selected for paraffin inclusion and histological examination. Chorioamnionitis was present more frequently in preterm adenovirus‐positive placentas compared to preterm adenovirus‐negative placentas (75% vs. 36%; P = 0.026) as well as compared to term adenovirus‐positive placentas (75% vs. 19%; P = 0.003). This study demonstrates that adenovirus infection of the placenta is associated strongly with histological chorioamnionitis and preterm birth. J. Med. Virol. 82:1379–1383, 2010. © 2010 Wiley‐Liss, Inc.     

High risk of spontaneous preterm birth among infants with gastroschisis

We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34–36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Over 44.5% of infants with gastroschisis were born preterm because of spontaneous etiologies; notably, 8.4% of infants with gastroschisis were born <34 weeks because of spontaneous etiologies (adjusted RRs 9.1–12.2). Overall, 53.7% of infants with gastroschisis were born preterm compared with only 6.9% of infants without gastroschisis (adjusted RR 15.2, 95% CI 13.6–19.5) and are at particularly high risk of spontaneous PTB. Nearly 9% of infants with gastroschisis delivered <34 weeks, regardless of preterm etiology, indicating that these infants are at great risk for PTB morbidities in addition to the complications from gastroschisis.     

Fetal size at the 32nd gestational week is associated with the risk of breech presentation at term birth

Objectives

The association patterns between breech presentation at birth and fetal biometry at the first, second, and third trimesters, newborn size but also maternal age, body height, prepregnancy weight status as well as gestational weight gain, were analyzed using a dataset of 4501 singleton term birth in Vienna, Austria.

Methods

In this medical record-based study, fetal biometry was reconstructed based on the results of three ultrasound examinations conducted at the 11th/12th, 20th, and 32nd gestational weeks. Head dimensions, abdominal dimensions, and femur length were determined by sonography. Birth weight, birth length, and head circumference were measured immediately after birth.

Results

The total breech presentation rate at birth was 6.2%. Breech newborns were significantly (p < 0.001) shorter and lighter at the time of birth, their head circumferences, however, were significantly larger (p = 0.001). At the 32nd week, breech fetuses showed significantly smaller biparietal breadths, but highly significantly longer heads. Their abdominal dimensions were significantly smaller, and their femora were shorter. Higher maternal age, and a longer, but narrower fetal head as well as smaller abdominal dimensions at the 32nd gestational week were independently related to a higher risk of breech presentation at the time of birth.

Conclusions

Fetuses who remain in a breech presentation until term birth (≥37 gestational weeks) differed significantly in head and abdominal dimensions from cephalic fetuses from the 32nd gestational week onwards.     

Timing is everything: A reconsideration of fetal growth velocity patterns identifies the importance of individual and sex differences

Fetal growth has been posited to follow a “timing hypothesis” sequence in which the second trimester favors a single growth velocity peak in body length and the third trimester accommodates a single growth velocity peak in weight accrual. To our knowledge, this proposition has never been tested with high‐frequency longitudinal ultrasound data from normally growing human fetuses. The present study examined whether fetal growth in leg length had its peak velocity at or about 20–26 gestational weeks and declined subsequently and whether estimated fetal weight velocity was maximal at or about 33 weeks and declined subsequently; if the greatest acquisition of leg length occurred in the second trimester and weight in the third trimester; and if birth outcomes reflected these relationships. The data in this study included approximately weekly longitudinal ultrasound data collected from 44 maternal/fetal pairs in Brussels, Belgium. Diaphyseal lengths of the femur and tibia provided information on leg growth and estimated fetal weight was assessed from the biparietal and occipital‐frontal head diameters and transverse and anterior–posterior diameters of the abdomen. Growth patterns were investigated from individual growth curves derived from daily growth velocity z‐scores. Paired t‐tests compared individuals' trimestral increments in leg length and fetal weight. Least‐squares regression models employing the robust procedure for repeated measurements were used to test for relationships between trimester, size, growth rates, and birth outcome, controlling for day of measurement, sex, maternal smoking, and gestational age at birth. The normal fetuses in this study grew by pulsatile patterns of leg and estimated weight acquisition, not a single peak and decline process. Greater incremental growth in estimated fetal weight occurred during the second trimester and leg length in the third trimester. Individual and sex effects were significant in growth velocity patterns. Girls grew with greater synchrony between leg and weight growth and were accelerated by comparison with boys, with faster leg growth predicting lower ponderal index by the second trimester. Birth outcomes were sex‐specific in timing effects and predictive variables. These results support the importance of sex‐specific analyses, reemphasize the common notion that girls grow faster than boys, and direct attention to cross‐talk between energy resources and growth. Am. J. Hum. Biol. 15:667–680, 2003. © 2003 Wiley‐Liss, Inc.     

Self‐reported illness and birth weight in the Philippines: Implications for hypotheses of adaptive fetal plasticity

It has been proposed that prenatal nutrition provides the fetus with a cue allowing it to adjust biological settings in anticipation of postnatal nutrition. To evaluate the reliability of fetal growth rate as a nutritional cue, this study assesses the extent to which a nonnutritional factor‐maternal illness symptoms during pregnancy‐predicts birth outcomes in a large, population‐based sample of Filipino women and their newborns (n = 2,887). Self‐reported illness symptoms were collected during pregnancy and used to predict weight, length, BMI, and gestational age at birth. Independent of potential confounders, number of reported symptoms predicted a significant dose‐response decrease in birth weight and BMI, but not length that reflected a combination of reduced fetal growth rate and reduced duration of gestation. These effects were comparable in male and female offspring, but tended to be stronger when reported closer to term. Among women interviewed at 32 weeks gestation or later, multiple symptoms predicted a 144 g birth weight reduction compared with no symptoms. These findings suggest an acute effect of maternal illness on fetal nutrition late in gestation when growth rate and fat deposition are most rapid. Although modest, the effect was larger than that of most pregnancy macronutrient supplementation trials. These findings using crosssectional, self‐reported illness symptoms highlight a nonnutritional maternal influence on fetal nutrition, which could attenuate its value as a cue of postnatal ecology. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Anthropometric characteristics of pregnant women in Cali,Colombia and relationship to birth weight

Anthropometric dimensions were collected from 46 pregnant women living in Cali, Colombia to gain a better understanding of how poor, urban women deal with the demands of pregnancy and to identify relationships between maternal characteristics and infant birth weight. Height, weight, skinfold thicknesses (subscapular, suprailiac, thigh, calf, and triceps), and circumferences (hip, thigh, calf, and mid‐upper arm) were measured on all women. Infant measurements were weight and length. The women were measured in the second and third trimesters, and a sub‐sample (n = 16) was measured twice in the third trimester. Mean birth weight was 3,137.6 ± 488.5 g (n = 44), and mean length was 49.8 ± 3.0 cm. All but three of the infants were full‐term, and the incidence of low birth weight (LBW) was 9%. The 46 women showed a significant increase in weight (P < 0.001); subscapular, suprailiac, and mid‐thigh skinfold thicknesses (P ≤ 0.01) and in hip, thigh, and calf circumferences (P ≤ 0.01) between trimesters 2 and 3. Women who gave birth to both normal birth weight (NBW) and LBW infants showed significant increases in weight (P < 0.001 and P = 0.02, respectively), but only women who had NBW infants showed significant increases in the suprailiac skinfold and hip circumference (P < 0.001). In the third trimester, attained weight, skinfold thicknesses, and circumferences tended to be greater in women who had NBW infants. In general, this group of women gained less weight and had a greater incidence of LBW infants compared with women in developed countries, but changes in skinfold thicknesses over the course of pregnancy were similar compared with other studies. Am. J. Hum. Biol. 14:29–38, 2002. © 2002 Wiley‐Liss, Inc.     

ORIGINAL ARTICLE: Activation of the Alternative Pathway of Complement is a Feature of Pre‐Term Parturition but not of Spontaneous Labor at Term

Citation Vaisbuch E, Romero R, Erez O, Mazaki‐Tovi S, Kusanovic JP, Soto E, Dong Z, Chaiworapongsa T, Kim SK, Ogge G, Pacora P, Yeo L, Hassan SS. Activation of the alternative pathway of complement is a feature of pre‐term parturition but not of spontaneous labor at term. Am J Reprod Immunol 2010; 63: 318–330 Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre‐term delivery <34 weeks of gestation. The aim of this study was to determine whether spontaneous pre‐term labor (PTL) with intact membranes, intra‐amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of study This cross‐sectional study included women in the following groups: (i) non‐pregnant (n = 40); (ii) normal pregnancy (gestational age range 20–36, 6/7 weeks, n = 63); (iii) women at term not in labor (n = 70); (iv) women at term in spontaneous labor (n = 59); (v) patients with an episode of PTL who delivered at term (n = 62); (vi) PTL without IAI who delivered pre‐term (n = 30); and (vii) PTL with IAI who delivered pre‐term (n = 67). Maternal plasma FBb concentrations were determined by ELISA. Results (i) Among patients with PTL, those who had a pre‐term delivery either with IAI (1.21 μg/mL, IQR 0.77–2.16) or without IAI (1.13 μg/mL, IQR 0.92–2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 μg/mL, IQR 0.64–1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre‐term (P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non‐pregnant controls (P = 0.8) and were not correlated with advancing gestational age (r = ?0.28, P = 0.8). Conclusion (i) Pre‐term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre‐term and term labors have fundamental differences in the regulation of innate immunity.     

CD8+ T cells in fetal membranes display a unique phenotype,and their activation is involved in the pathophysiology of spontaneous preterm birth

Preterm labor/birth is the leading cause of perinatal mortality and morbidity worldwide. Previous studies demonstrated that T cells were crucial for maintaining maternal–fetal immune tolerance during the first trimester of pregnancy; however, their phenotypes and functions in labor and delivery remain largely unknown. We recruited three cohorts of women at delivery for T-cell immunophenotyping in the placentas, fetal membranes, umbilical cord blood, and maternal peripheral blood. Our data showed a differential enrichment of T cells during the third trimester of human pregnancy, with CD4⁺ T cells being more observable within the umbilical cord blood, whereas CD8⁺ T cells became relatively more abundant in fetal membranes. CD4⁺ and CD8⁺ T cells derived from fetal membranes were dominated by effector memory T cells and exhibited extensive expression of activation markers but decreased expression of homing receptor. In comparison with term births, fetal membrane CD8⁺ T cells, especially the central memory subset, were significantly increased in frequency and showed more profound activation in spontaneous preterm birth patients. Finally, using an allogeneic mouse model, we found that T-cell-activation-induced preterm birth could be alleviated by the depletion of CD8⁺ T but not CD4⁺ T cells in vivo. Collectively, we showed that CD8⁺ T cells in fetal membranes displayed a unique phenotype, and their activation was involved in the pathophysiology of spontaneous preterm birth, which provides novel insights into the immune mechanisms of preterm birth and potential targets for the prevention of this syndrome. © 2023 The Pathological Society of Great Britain and Ireland.     

Tibetan protection from intrauterine growth restriction (IUGR) and reproductive loss at high altitude

Chronic hypoxia at high altitude restricts fetal growth, reducing birth weight and increasing infant mortality. We asked whether Tibetans, a long‐resident high‐altitude population, exhibit less altitude‐associated intrauterine growth restriction (IUGR) and prenatal or postnatal reproductive loss than Han (ethnic Chinese), a group that has lived there for a shorter period of time. A population sample was obtained, comprising 485 deliveries to Tibetan or Han women over an 18‐month period at 8 general hospitals or clinics located at 2,700–4,700 m in the Tibet Autonomous Region, China. Birth weight, gestational age, and other information were recorded for each delivery. Prenatal and postnatal mortality were calculated using information obtained from all pregnancies or babies born to study participants. Tibetan babies weighed more than the Han, averaging 310 g heavier at altitudes 2,700–3,000 m (95% CI = 126, 494 g; P < 0.01) and 530 g heavier at 3,000–3,800 m (210, 750 g; P < 0.01). More Han than Tibetan babies were born prematurely. Prenatal and postnatal mortality rose with increasing elevation and were 3‐fold higher across all altitudes in the Han than the Tibetans (P < 0.05). Tibetans experience less altitude‐associated IUGR than Han and have lower levels of prenatal and postnatal mortality. When the relationships between birth weight and altitude are compared among these and other high‐altitude populations, those living at high altitude the longest have the least altitude‐associated IUGR. This may suggest the occurrence of an evolutionary adaptation. Am. J. Hum. Biol. 13:635–644, 2001. © 2001 Wiley‐Liss, Inc.     

Differences in mortality and morbidity according to gestational ages and birth weights in infants with trisomy 18

The aim of this study was to clarify the effects of gestational age and birth weight on outcomes of the infants. Medical records of 36 infants with trisomy 18 admitted to Tokyo Women's Medical University Hospital from 1991 to 2012 were reviewed retrospectively. We compared clinical characteristics between term infants (n = 15) and preterm infants (n = 21). There were one very‐low‐birth‐weight (VLBW) term infant (5%) and 12 VLBW preterm infants (80%). Although there were no significant differences in clinical characteristics and provided management between the two groups, none of the preterm infants achieved survival to discharge. On the other hand, 6 of 21 term infants (29%) achieved survival to discharge (P < 0.05). Similar results were obtained for comparisons between the VLBW infants and non‐VLBW infants. Multiple logistic regression analysis revealed that shorter gestational age had a more negative impact than lower birth weight to survival to discharge in infants with trisomy 18. In both preterm and term groups, the infants who died before 30 days commonly died of respiratory failure or apnea. Whereas, the infants who survived more than 30 days mostly died of heart failure. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.     

Polymorphisms in the Angiotensin Converting Enzyme Gene and Growth in the First Year of Life

Abnormal patterns of fetal and infant growth have been associated with an increased risk of cardiovascular disease in adulthood. Catch‐up growth during the first year of life has been associated with a higher prevalence of type 2 diabetes mellitus, whereas a lack of catch‐up growth tracks with a risk of hypertension. The role of genetic factors influencing both growth and blood pressure have not been explored. We genotyped cord blood samples from 530 singleton, Caucasian, uncomplicated pregnancies, drawn from a larger cohort of 1650 pregnancies, and related polymorphism in the angiotensin converting enzyme (ACE) gene (alleles insertion (I) or deletion (D)) with measures of size at birth and at age of 1 year. ACE genotype did not significantly influence size at birth, although there was a greater proportion of individuals with the D/D genotype born with a birth weight less than the 10^th centile (P = 0.004). The ACE I/I genotype was significantly associated with higher weight (p = 0.001), body mass index (p = 0.001) and mid arm circumference (p = 0.001) at 1 year of age compared to the ACE D/D and I/D genotypes. Individuals with the I/I genotype displayed catch‐up (gain from birth size of ≥0.6 Standard Deviation Score) in weight (p = 0.04), body mass index (p = 0.03) and mid arm circumference (p = 0.03) compared to the D/D group, the majority of which showed no change or catch‐down. The I/D genotype was distributed equally across the catch up/catch down/no change categories. The effect was more marked in males, but ACE genotype and sex of the infant contributed independently to mid arm circumference measurements and there was no interaction between the two. There was no effect of maternal or paternal ACE genotype on birth size. In a multiple linear regression model ACE genotype, socioeconomic status and sex of the infant explained 10.9% of the variance in body mass index SDS at 1 year of age. We conclude that the ACE I/I genotype is associated with a higher weight and body mass index SDS at 1 year of age, along with catch‐up in terms of these measures from birth to 1 year. The D/D genotype is associated with a greater proportion of babies, born at term, that at small for gestational age. These results suggest that due consideration should be given to the underlying genotype of an individual when evaluating the association of early human growth with the development of risk factors for cardiovascular disease. The observation of independent effects of genotype, sex of the individual and socioeconomic status on postnatal growth suggests the need to develop methodologies for the integration of genetic and environmental factors in causality modelling.