Maternal pre-eclampsia as a risk factor for necrotizing enterocolitis

Objective: Similar pro-inflammatory responses are present in pre-eclampsia (PE) and necrotizing enterocolitis (NEC). We hypothesized that maternal PE is an independent risk factor for the development of NEC.

Methods: A retrospective database of all live births (2008–2011) at a tertiary center was constructed. Infant and maternal characteristics were gathered. Babies born to mothers with or without PE were compared. Data were analyzed using Mann–Whitney U, Pearson's χ², binary logistic regression and relative risks.

Results: Incidence of NEC was 1.5% in non-PE and 4.6% in the PE group (p?<?0.001), but once controlled for gestational age and birth weight, the difference lost statistical significance. PE babies were more frequently preterm (41.4% versus 14.5%, p?<?0.001) and had intrauterine growth restriction (IUGR) (10.2% versus 6.3%, p?<?0.001). Within preterm babies, 9.0% of non-PE and 10.8% of PE babies developed NEC (p?=?0.25). Effect of PE was significant in sub-group of IUGR babies, with NEC in 1.5% of non-PE and 13.6% in PE babies (p?<?0.001).

Conclusions: Maternal PE is an independent risk factor for the development of NEC in some sub-groups of babies, most notably with IUGR. Fetal hypoxia caused by abnormal placentation in PE leads to restricted growth, and may be the underlying mechanism that predisposes the newborn to NEC.     

The association between customised small for gestational age infants and pre-eclampsia or gestational hypertension varies with gestation at delivery

OBJECTIVES: (1) To describe the association between small for gestational age (SGA) infants and pre-eclampsia (PE) and gestational hypertension (GH) and (2) to determine how this association changes with gestational age at delivery using customised centiles to classify infants as SGA. DESIGN: A retrospective observational study. SETTING: National Women's Hospital, a Tertiary Referral Centre in Auckland, New Zealand. POPULATION: A total of 17 855 nulliparous women delivering between 1992 and 1999. METHODS: A comparison of the number of women with a customised SGA infant, PE and GH according to gestational age at delivery. MAIN OUTCOME MEASURES: The incidence of SGA infants (defined as birthweight <10th customised centile), PE and GH at <34, 34-36(+6) and > or =37 weeks. RESULTS: A total of 1847 (10.3%) infants were SGA, 520 (2.9%) women had PE and 1361 (7.6%) had GH. SGA, PE and GH all occurred more commonly with increasing gestation at delivery with 85%, 62% and 90% of cases delivered at term. In women delivering SGA infants, coexisting PE was more likely to occur among those delivered preterm than at term (38.6% at <34 weeks [relative risk, RR 10.2 95%CI 7.3-14.4], 22.4% at 34-36(+6) weeks [RR 6.0 95%CI 4.1-8.6] and 3.8% at > or =37 weeks [OR 1.0]). Women with preterm PE were more likely to have a SGA infant than women with term PE (57.1% at <34 weeks [RR 3.1 95%CI 2.3-4.2], 31.7% at 34-36(+6) weeks [RR 1.7 95%CI 1.2-2.5]) and 18.3% at > or =37 weeks [OR 1.0]). There was a similar association between GH and SGA infants as gestation advanced (57.6% at <34 weeks [RR 4.8 95%CI 3.4-6.6], 30.5% at 34-36(+6) weeks [RR 2.5 95%CI 1.8-3.5] and 12.1% > or =37 weeks [OR 1.0]). CONCLUSIONS: SGA infants and PE are more likely to coexist in preterm births compared with term births. This is likely to reflect the degree of placental involvement in each disease process.     

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries

Objective  To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia.
Design  Multicentred, randomised, controlled, double-blinded trial.
Setting  Antenatal care clinics and Hospitals in four countries.
Population  Pregnant women between 14 and 22 weeks' gestation.
Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.
Main outcome measures  Pre-eclampsia, low birthweight, small for gestational age and perinatal death.
Results  Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.
Conclusion  Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.     

Telomere length in small-for-gestational-age babies

OBJECTIVE: Short telomeres are associated with adult cardiovascular disease. Our aim was to determine whether small-for-gestational-age (SGA) newborns have shortened telomeres compared with appropriately grown controls. DESIGN: Prospective cohort study. SETTING: Large tertiary referral unit in Trent, UK. POPULATION: Seventy-two women who delivered at 35-42 weeks of gestation were recruited; 34 delivered SGA babies (less than or equal to the third birthweight centile) and 38 had appropriately grown babies (greater than the tenth centile). METHODS: Maternal and cord blood samples were collected at delivery. A Southern blot of DNA from these samples was hybridised with a 32P-labelled telomeric probe and telomere length was measured. MAIN OUTCOME MEASURES: Mean maternal and newborn telomere length. RESULTS: Maternal and newborn telomere lengths were significantly correlated in both the SGA and the control groups (r2 = 0.25, P < 0.0001). Telomere lengths were similar in both maternal (control 8.41 +/- 0.9 kb versus SGA 8.29 +/- 1.0 kb, P = 0.57) and newborn (control 10.36 +/- 1.5 kb versus SGA 10.33 +/- 1.3 kb, P = 0.93) cohorts in the two groups. CONCLUSIONS: Intrauterine events associated with impaired fetal growth do not appear to be associated with increased telomere shortening.     

The effects of labor on infant mortality among small-for-gestational-age infants in the USA

Objective: To determine whether the presence of labor affects infant mortality among small-for-gestational-age (SGA) infants. Methods: Data were derived from the United States national linked birth/infant death data sets for 1995–97. Singleton SGA live births in cephalic presentation delivered at 24–42 weeks' gestation were included. Mortality rates for SGA infants exposed and unexposed to labor were compared, and relative risks (RR) were derived using multivariable logistic regression models, after adjusting for potential confounding factors. Results: Of 986 405 SGA infants, 87.4% were exposed to labor. Infants exposed to labor at 24–31 weeks had greater risks of dying during the early neonatal period (RR 1.79-1.86). Decreased risks of late and postneonatal death were observed at all gestational ages in the presence of labor. Conclusions: Exposure to labor is associated with an increased risk of early neonatal death among SGA infants, especially at gestational ages below 32 weeks. Future randomized trials are warranted to determine the optimal obstetric management of these high-risk infants.     

Long-term cardiovascular hospitalizations of small for gestational age (SGA) offspring born to women with and without gestational diabetes mellitus (GDM)‡

Abstract

Objective: To assess whether delivery of small for gestational age (SGA) neonates to mothers with gestational diabetes mellitus (GDM) increases the risk of long-term cardiovascular offspring hospitalizations compared to SGA neonates born to mothers without GDM. Study design: This is a population-based retrospective cohort study. The study group was SGA offspring born to mothers with GDM (n?=?259), while the control group was SGA offspring born to mothers without GDM (n?=?9053). The main factor evaluated was offspring cardiovascular hospitalizations up to the age of 18?years. Kaplan-Meier survival curve was used to estimate cumulative incidence of cardiovascular hospitalizations. A Cox proportional hazards model was used to estimate the adjusted hazard ratios (HR) for cardiovascular hospitalizations. Results: SGA children born to mothers with GDM had significantly higher rates of cardiovascular-related hospitalizations (1.9% vs. 0.7%, p?=?.026). A Kaplan-Meier survival curve demonstrated that SGA children born to GDM mothers had a higher cumulative incidence of cardiovascular hospitalizations (log-rank p?=?.037). The Cox regression model, while controlling for confounders, demonstrated that delivery of SGA neonates to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations (adjusted HR =2.6; 95% CI 1.02–6.55 p?=?.045). Conclusion: Delivery of SGA neonates born to mothers with GDM is independently associated with long-term cardiovascular offspring hospitalizations.     

The bone mineral density change with aging of Japanese women measured by single energy X-ray absorptiometry and dual energy X-ray absorptiometry

Summary The calcaneus bone mineral density of 473 Japanese women was measured by single energy X-ray absorptiometry (SXA) and the verterae bone mineral density of 198 Japanese women was measured by dual energy X-ray absorptiometry (DEXA). The calcaneous bone mineral density of Japanese women starts decreasing from age 30, and the rate of decrease accelerates from the age of 50. The vertebrae bone mineral density starts decreasing from the age of 35, and a conspicuous decrease can be seen from the age of 50 as well. Because bone deterioration of Japanese women is thought to start earlier than Caucasian, the necessity of osteoporosis screening before menopause was suggested. A high positive correlation (r=0.804) between calcaneus bone mineral density and vertebrae bone mineral density was found, and a high degree of precision of SXA was shown.     

Maternal plasma concentrations of the placental specific sFLT-1 variant,sFLT-1 e15a,in fetal growth restriction and preeclampsia

Objective: sFLT-1 e15a is a recently described sFlt-1 variant that is placental and primate specific. As such, it may have potential as a biomarker. Using a newly developed ELISA, we measured maternal plasma sFLT-1 e15a levels in women with fetal growth restriction and pre-eclampsia.

Method: We performed a nested case-control study where we measured total sFLT-1 and sFLT-1 e15a plasma protein concentrations. Samples, selected from a prospective cohort study, consisted of 87 healthy controls, 11 cases that developed term preeclampsia and 20 cases where there was fetal growth restriction. We also measured sFLT-1 and sFLT-1 e15a plasma concentrations in a separate cohort: 15 cases of preterm preeclampsia and 24 healthy controls.

Results: The prospective case-control cohort demonstrated significantly increased sFLT-1 e15a among cases with term fetal growth restriction (p?p?p?Conclusion: Plasma sFLT-1 e15a is significantly increased in early-onset preeclampsia and term fetal growth restriction. Further assessment of the benefit for sFLT-1 e15a testing in prediction or diagnosis of these disease states is warranted.     

Prediction of fetal birthweight in Taiwanese women with pre-eclampsia and gestational hypertension using an equation based on maternal characteristics

Aim:  The purpose of the present study was to develop a method for predicting the birthweight of newborns in women with pre-eclampsia and gestational hypertension based on maternal characteristics and pregnancy-related factors.
Methods:  A total of 661 consecutive pregnant women with pre-eclampsia and gestational hypertension who delivered at Chang Gung Memorial Hospital from 1994 to 2003 were included in the analysis. Multivariate regression formulas (Models I and II) were derived from maternal characteristics to predict low infant birthweight. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated and tested for these formulas.
Results:  The Model I formula was as follows:

Using a cut-off value of 2210 g, the equation predicts the occurrence of a low birthweight baby with 90.9% sensitivity. If higher specificity is required, increasing the cut-off value to 2488 g yields a specificity of 95.2%. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 93.7 (95% confidence interval [CI], 0.88 to 0.99) for low birthweight baby prediction in Model I.
Conclusion:  The results suggest that these regression formulas based on maternal characteristics may accurately predict low birthweight babies in pregnant women with pre-eclampsia and gestational hypertension. The cut-off values were determined and cross-validated by ROC curve analysis.     

Obstetric and perinatal outcome in women with twin pregnancy and gestational diabetes

Objective: The aim of this study was to evaluate pregnancy complications and obstetric and perinatal outcomes in women with twin pregnancy and GDM. Study Design: An observational multicentre retrospective study was performed and 534 pregnant woman and 1068 twins infants allocated into two groups, 257 with GDM and 277 controls, were studied. Main Outcome Measures: Pregnant women characteristics, hypertensive complications, preterm delivery rate, mode of delivery and birthweight were analysed. Results: Pregnant women with GDM were older (p?<?0.001) and had higher body mass index (p?<?0.001) than controls. GDM was associated with higher risk of prematurity in twin pregnancy (odds ratio 1.64, 95% confidence interval [1.14–2.32], p?=?0.005). This association was based on the association with other pregnancy complications. Birthweight Z-scores were significantly higher in the GDM group (p?=?0.02). The rate of macrosomia was higher in the GDM group (p?=?0.002) and small for gestational age (SGA) babies were significantly less frequent (p?=?0.03). GDM was an independent predictor of macrosomia (p?=?0.006). Conclusion: The presence of GDM in twin pregnancy was associated with a higher risk of hypertensive complications, prematurity and macrosomia, but significantly reduces the risk of SGA infants. Prematurity was related to the presence of other associated pregnancy complications.     

Pathological examination of the placenta in small for gestational age (SGA) children with or without postnatal catch-up growth

Background/objective: Approximately 10% of small for gestational age (SGA) infants fail to catch up. The relationship between postnatal growth and placental pathology in SGA infants remains unclear. Our aim was to assess the involvement of placental pathology in postnatal growth of SGA infants.

Methods: We retrospectively evaluated placental pathology and postnatal growth in single-pregnancy infants born after 37 gestational weeks in our institution, with both birth weight and length below ?2 standard deviation scores (SDS) of the normal weight and length. “Catch-up” was defined as height reaching ?2 SDS before the second birthday. Pathology of the placenta was classified into: abnormality due to maternal factors or fatal factors, villitis of unknown etiology (VUE), other abnormalities and no abnormality.

Results: Of the 33?084 infants, 142 met our criteria and 49 of them had analyzable data. The overall catch-up rate was 84%. Catch-up growth took place in all infants with no placental abnormality and only 57% of infants with abnormality due to fatal factors. There was no significant relationship between catch-up rate and other factors.

Conclusion: Placental pathology is associated with postnatal growth in SGA children born at term. Placental abnormality due to fetal factors is related to poor catch-up rate.     

The utility of ultrasound in late pregnancy compared with clinical evaluation in detecting small and large for gestational age fetuses in low-risk pregnancies

Objective: To determine the utility of ultrasound (US) in late pregnancy for identifying fetuses with growth disturbances.

Methods: This study was designed as a retrospective study of birth weights over a 12-month period at the Royal Hobart Hospital (RHH) and Barwon Health (BH). Data were collected from the discharge summaries and medical records at both hospitals targeting abnormal fetal weight below 10th percentile (small for gestational age – SGA) and above 90th percentile (large for gestational age – LGA).

Results: There were 4079 study patients from both hospitals. After weight adjustment by gender and gestational age, an abnormal fetal weight was detected in 741 cases (babies over the 90th percentile or below 10th percentile). One hundred and twenty-eight patients with high-risk pregnancies were excluded. Therefore, a total of 613 patients remained that were considered to be low-risk pregnancies with abnormal foetal growth; 305 patients from RHH and 308 from BH. The antenatal detection rate for LGA was 35.9%, at RHH by combination of US and clinical evaluation, while for BH it was 34.8% by clinical evaluation alone (p?=?0.910). The antenatal detection rate for SGA was 36.8% via US and clinical evaluation at RHH and 54.5% by clinical evaluation alone at BH (p?=?0.006).

Conclusion: This study shows no benefit in the use of routine US for the antenatal diagnosis of LGA compared with clinical evaluation in low-risk pregnancies. US evaluation was inferior to clinical evaluation in the antenatal diagnosis of SGA in low-risk pregnancies.     

High prevalence of vitamin D deficiency among pregnant women in a Turkish population and impact on perinatal outcomes

Objective: Maternal vitamin D deficiency is a major public health problem. The aim of this study is to investigate the influence of vitamin D deficiency on perinatal results in primigravida.

Methods: One-hundred fifty-two healthy nullipar women were included in the study. Pregnant women with serum vitamin D levels <15ng/ml were defined as Group I and ≥15?ng/dl were defined as Group II; data were evaluated retrospectively. Type of delivery, gestational age at birth, birth weight, intensive care of the newborn, peri-and postpartum complications were recorded. Statistical analyses were performed with SPSS for Windows (version 16.0 ). Categorical variables were assessed using chi-squared test. The numeric variables were analyzed using Student's t-test and one-way ANOVA.

Results: 44.6% of pregnant women were found to have vitamin D deficiency. The mean serum vitamin D levels for Groups I and II were 10.8?±?3.8 and 23.8?±?13.3?ng/ml, respectively. SGA deliveries were detected in 16.66% and 4.87% of the primigravidas with and without vitamin D deficiency, respectively.

Conclusions: This study has shown that maternal vitamin D deficiency is related with an increased risk of SGA delivery. Further studies are needed to explain the relationship with vitamin D deficiency and poor perinatal outcomes.     

Circulating fetal and total cell-free DNA,and sHLA-G in black South African women with gestational hypertension and pre-eclampsia

Objective: Quantification of circulating fetal and total cell-free DNA (cfDNA) and soluble human leucocyte antigen (HLAG) in gestational hypertension and pre-eclampsia.

Methods: Serum cfDNA were quantified in controls, pre-eclamptics, and gestational hypertensive patients using real-time qPCR. Soluble HLAG was measured by enzyme-linked immune-sorbent assay.

Results: Serum fetal and total cfDNA levels were higher in pre-eclampsia compared with the controls and gestational hypertensives (p < 0.001), more so in severe compared with mild-to-moderate pre-eclampsia (p < 0.05). Soluble HLAG levels were lower in pre-eclamptics than controls and gestational hypertension (p < 0.05).

Conclusion: Circulating fetal and total cfDNA were increased, while soluble HLAG was decreased in pre-eclampsia.     

Hypertension during pregnancy in South Australia, part 1: pregnancy outcomes

BACKGROUND: There have been conflicting reports about pregnancy outcome in the hypertensive disorders of pregnancy. The present study was undertaken to examine outcomes using a population database. AIMS: To examine for differences in a range of pregnancy outcomes between three different groups of hypertensive women and normotensive women in South Australia. METHODS: Nine pregnancy outcomes were compared for 70,386 singleton pregnancies in the South Australian perinatal data collection in 1998-2001, consisting of 639 women with pre-existing hypertension, 5356 women with pregnancy hypertension, 448 women with superimposed pre-eclampsia and 63 943 normotensive women. Means for the four groups were calculated for birthweight, gestational age, the baby's and mother's length of stay. The groups were also compared for perinatal deaths with an earlier period, 1991-1997. RESULTS: While all three hypertensive groups had high incidences of induction of labour and emergency Caesarean, only pre-existing hypertension and superimposed pre-eclampsia were significantly associated with elective Caesarean section. All hypertensive groups had increased risks for low birthweight and preterm birth and special and neonatal intensive care. Uncomplicated pre-existing hypertension was not associated with small for gestational age infants, but with preterm delivery between 32 and 36 weeks' gestation. Superimposed pre-eclampsia had the worst prognosis for perinatal and maternal morbidity. While pregnancy hypertension held the intermediate position, it was not associated with an increase in perinatal mortality. The perinatal mortality rate for women with hypertensive disorders in 1998-2001 was significantly lower than that of an earlier period and equivalent to that for normotensive women. CONCLUSIONS: Superimposed pre-eclampsia occurs in approximately 40% of pregnancies of women with pre-existing hypertension and has the most severe outcomes. The hypertensive disorders are associated with high levels of morbidity and intervention, but the high perinatal mortality associated with these disorders has fallen significantly.