DESIGN: A prospective study.
SETTING: A tertiary hospital in Malaysia.
POPULATION: A cohort of 193 term nulliparous women with intact membranes.
METHODS: Prior to labour induction, cervical fluid was obtained via a vaginal speculum and tested for IGFBP-1, followed by TVUS and finally Bishop score. After each assessment the procedure-related pain was scored from 0 to 10. Cut-off values for Bishop score and cervical length were obtained from the receiver operating characteristic (ROC) curve. Multivariable logistic regression analysis was performed.
MAIN OUTCOMES MEASURES: Vaginal delivery and vaginal delivery within 24 hours of starting induction.
RESULTS: Bedside IGFBP-1 testing is better tolerated than Bishop score, but is less well tolerated than TVUS [median (interquartile range) of pain scores: 5 (4-5) versus 6 (5-7) versus 3 (2-3), respectively; P < 0.001]. IGFBP-1 independently predicted vaginal delivery (adjusted odds ratio, AOR 5.5; 95% confidence interval, 95% CI 2.3-12.9) and vaginal delivery within 24 hours of induction (AOR 4.9; 95% CI 2.1-11.6) after controlling for Bishop score (≥4 or ≥5), cervical length (≤29 or ≤27 mm), and other significant characteristics for which the Bishop score and TVUS were not predictive of vaginal delivery after adjustment. IGFBP-1 has 81% sensitivity, 59% specificity, positive and negative predictive values of 82 and 58%, respectively, and positive and negative likelihood ratios of 2.0 and 0.3 for vaginal delivery, respectively.
CONCLUSION: IGFBP-1 better predicted vaginal delivery than BS or TVUS, and may help guide decision making regarding labour induction in nulliparous women.
TWEETABLE ABSTRACT: IGFBP-1: a stronger independent predictor of labour induction success than Bishop score or cervical sonography.
OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.
SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.
SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.
DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia.
AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.
METHODS: Chorionic arteries and veins were isolated from human placenta from normal, gestational diabetes mellitus and type 1 diabetes mellitus pregnancies. Isometric tension recording measured responses to adenosine and the thromboxane A2 analogue U46619 (thromboxane A2 mediates fetoplacental vasoconstriction to adenosine). Adenosine and thromboxane prostanoid receptor protein expression was determined by immunoblotting.
RESULTS: Adenosine elicited contractions in chorionic arteries and veins which were impaired in both gestational diabetes mellitus and type 1 diabetes mellitus. Contractions to potassium chloride were unchanged. Adenosine A2A and A2B receptor protein levels were not different in gestational diabetes mellitus and normal pregnancies. Contractions to U46619 were unaltered in gestational diabetes mellitus arteries and increased in type 1 diabetes mellitus arteries. Overnight storage of vessels restored contractility to adenosine in gestational diabetes mellitus arteries and normalized contraction to U46619 in type 1 diabetes mellitus arteries.
CONCLUSION: These data are consistent with the concept of aberrant adenosine signalling in diabetes; they show for the first time that this involves impaired adenosine contractility of the fetoplacental vasculature.
METHODS: This non-blinded, randomized clinical trial included 228 pregnant women at term with obstetric or medical indications for induction of labour. Women either took 50 µg misoprostol orally (two 25 µg tablets) or had one 25 µg tablet of misoprostol inserted in the posterior vaginal fornix. In each group, misoprostol administration was repeated every four hours in the same dose until regular uterine contractions were established or to a maximum of five doses. Time to delivery and outcome data for each group were compared.
RESULTS: Of the 228 women, eight (3.5%) were excluded from the analysis as they withdrew their consent after randomization. Mean induction-to-delivery interval was similar in both groups (21.22 hours in the oral group vs. 20.15 hours in the vaginal group; P = 0.58). There was no significant difference between the groups with respect to the number of women who delivered within 24 hours or who required oxytocin augmentation of labour, the mode of delivery, and neonatal outcomes (P > 0.05). Uterine hyperstimulation occurred in two women who received misoprostol vaginally, but not in any of the women in the oral misoprostol group.
CONCLUSION: Oral misoprostol in a dose of 50 µg every four hours, to a maximum of five doses, has the potential to induce labour as safely and effectively as 25 µg misoprostol administered vaginally every four hours.
MATERIALS AND METHODS: A cross-sectional study was conducted to measure D-dimer in healthy pregnant women, and a non-pregnant control group, using the quantitative HaemosIL D-dimer HS500 assay. Reference ranges were derived using CLSI 'Robust' methods, and differences between group medians were tested using the Kruskal-Wallis and Mann-Whitney U tests.
RESULTS: Plasma D-dimer levels were measured in 92 pregnant women (distributed across the three trimesters)and 31 control women. The medians (and reference ranges) in ng/mL were: control 265 (<799); first trimester 481 (<1070); second trimester 1073 (357-1748); 3rd trimester 1533 (771-2410). There were significant differences between the D-dimer levels of each group and each of the other groups (P<0.001).
CONCLUSIONS: Reference ranges for D-dimer in pregnant Malaysian women have been establised by this study. Whether these ranges can be used to determine cut-off levels for the exclusion of VTE at different stages of pregnancy is doubtful, as the levels rise continuously through pregnancy, and some very high outlying values occur in apparently normal near-term pregnancy.
METHODS: An analysis of observational data was conducted using live, singleton, term births recorded in the Malaysian National Obstetrics Registry between 2010 and 2012. A total of 272,472 live, singleton, term births without congential anomalies were recorded, of which 1,580 (0.59%) had 1 min Apgar scores <4. Descriptive methods and bi- and multi-variable logistic regression were used to identify risk factors associated with recovery (5 min Apgar score ≥7) from 1 min Apgar scores <4.
RESULTS: Less than 1% of births have a 1 min Apgar scores <4. Only 29.4% of neonates with 1 min Apgar scores <4 recover to a 5 min Apgar score ≥7. Among uncomplicated vaginal deliveries, after controlling for other factors, deliveries by a doctor of neonates with a 1 min Apgar score <4 had odds of recovery 2.4 times greater than deliveries of neonates with a 1 min Apgar score <4 by a nurse-midwife. Among deliveries of neonates with a 1 min Apgar score <4 by doctors, after controlling for other factors, planned and unplanned CS was associated with better odds of recovery than uncomplicated vaginal deliveries. Recovery was also associated with maternal obesity, and there was some ethnic variation - in the adjusted analysis indigenous (Orang Asal) Malaysians had lower odds of recovery.
CONCLUSIONS: A 1 min Apgar score <4 is relatively rare, and less than a third recover by five minutes. In those newborns the qualification of the person performing the delivery and the type of delivery are independent predictors of recovery as is maternal BMI and ethnicity. These are associations only, not necessarily causes, and they point to potential areas of research into health systems factors in the labour room, as well as possible biological and cultural factors.