Neonatal vitamin K prophylaxis in Great Britain and Ireland: the impact of perceived risk and product licensing on effectiveness.

OBJECTIVE: To determine current use of vitamin K (VK) prophylaxis in newborns and review the efficacy and effectiveness of regimens used. DESIGN: Efficacy and effectiveness calculated using current practice details, data from Southern Ireland and two previous surveys, together with contemporaneous studies of vitamin K deficiency bleeding (VKDB). SETTING: Current survey: United Kingdom (Great Britain and Northern Ireland). Efficacy and effectiveness tables: United Kingdom and Southern Ireland. MAIN OUTCOME MEASURES: Current VK prophylaxis following uncomplicated term deliveries. Relative risk of VKDB calculated for the VK actually received and for "intention to treat". RESULTS: Questionnaire response rate 95% (n = 243), all recommending VK prophylaxis. No association between unit size and route of administration. For uncomplicated term deliveries, 60% recommended intramuscular (IM) prophylaxis, 24% oral and 16% offered both routes without bias. All units offering IM gave a single dose, mostly 1 mg Konakion Neonatal. Oral regimens showed more variation: two thirds gave 2 mg (range 0.5-2 mg), the number of doses ranged from 1 to 11 and many used preparations off-licence or the unlicensed Orakay. IM prophylaxis, if given, provided the best protection (most efficacious) against VKDB. However, on an intention-to-treat basis (effectiveness), there is no statistically significant difference between the risks of VKDB after intended IM VK and after oral prophylaxis intended to continue beyond a week. CONCLUSIONS: Although the principles of VK prophylaxis is now accepted by all, there is no uniformity in practice. Omission of prophylaxis appears to be a greater problem for IM than for multi-dose oral prophylaxis, affecting overall effectiveness.     

Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02

Objective

To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988–90 survey (VKDB‐90).

Design

Two 2‐year surveys conducted during 1993–4 (VKDB‐94) and 2001–02 (VKDB‐02).

Setting

Data collected from all consultant paediatricians in Great Britain and Ireland.

Patients

All infants presenting with bleeding resulting from vitamin K (VK) deficiency.

Main outcome measures

Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features.

Results

Compared with previous studies, VKDB‐02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long‐term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast‐fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB‐90, 10 of 32 in VKDB‐94 and 4 (because of parental refusal) of 7 in VKDB‐02. Seven received one oral dose of VK in VKDB‐90, 16 in VKDB‐94 and none in VKDB‐02. Underlying liver disease was found in six cases in VKDB‐90, 12 in VKDB‐94 and one in VKDB‐02.

Conclusions

In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast‐fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.     

Vitamin K prophylaxis and late vitamin K deficiency bleeding in infants: Fifth nationwide survey in Japan

Background: In 1980, the first nationwide survey on late vitamin K deficiency bleeding (VKDB) in infants was conducted in Japan, and it was followed by the second, third and fourth nationwide surveys in 1985, 1988 and 1991, respectively. The fifth nationwide survey was designed to ascertain the epidemiology of late VKDB between January 1999 and December 2004. Patients and methods: Questionnaires were sent to 2161 hospitals in Japan that employed members of the Japan Pediatric Society in March 2005. Responses were received from 1373 hospitals, for a response rate of 63.5%. Results: The total number of reported cases was 71, including 21 idiopathic type and 16 secondary type. The incidence of late VKDB was estimated to be 1.9 cases per 100 000 births (95% confidence interval: 1.2–3.0) during this survey period. In 34 cases, the presence or absence of any underlying disease was not clarified. A total of 67/71 infants were entirely breast‐fed. Intracranial hemorrhaging was observed in 26 (63.4%) out of 41 infants whose bleeding sites were described in the questionnaires. In 63 cases (88.7%) of late VKDB found in the present survey, however, vitamin K had been given at least once either during or after the neonatal period. Conclusions: A reevaluation of the current prophylaxis strategy for late VKDB in infants is necessary.     

Plasma concentrations of vitamin K1 and PIVKA-II in bottle-fed and breast-fed infants with and without vitamin K prophylaxis at birth

Plasma vitamin K₁ and proteins induced by vitamin K absence (PIVKA) were assayed simultaneously 1–4 days and 29–35 days after delivery in three groups of infants: breast-fed not receiving vitamin K at birth (n=12), bottle-fed without vitamin K administration at birth (n=7) and breast-fed receiving 1 mg vitamin K₁ administered by intramuscular injection at birth (n=13). The bottle-fed infants had a significantly higher vitamin K₁ plasma level than breast-fed infants who did not receive vitamin K₁ at birth. Extremely high levels of vitamin K were obtained 1–4 days after intramuscular administration. At the age of 1 month, breast-fed infants had the same plasma vitamin K₁ concentration whether or not they had received vitamin K₁ supplements. Decarboxy prothrombin (PIVKA-II) a reliable indicator of biochemical vitamin K deficiency, was found in 5 out of 12 breast-fed and in 2 out of 6 bottle-fed infants who had not received supplemental vitamin K₁ after birth. In a separate study, we followed up to 90 days after birth a larger group if infants. PIVKA-II was found with significantly greater frequency in breast-fed infants receiving no vitamin K than in breast-fed infants receiving 1 mg vitamin K intramuscularly at birth, or in bottle-fed infants without extra vitamin K₁. These data form a strong argument for routine vitamin K prophylaxis after birth for all breast-fed infants. The optimum dose and manner of administration require further study.Abbreviations PIVKA proteins induced by vitamin K absence - PIVKA-II decarboxy prothrombin - AU arbitrary units     

New Zealand surveillance of neonatal vitamin K deficiency bleeding (VKDB): 1998-2008

Aim: To undertake surveillance of vitamin K deficiency bleeding (VKDB) from 1998, through the transition to a new single licensed vitamin K preparation in 2001, to 2008. Methods: VKDB was listed with other rare conditions on the card sent monthly to registered specialist paediatricians by the New Zealand Paediatric Surveillance Unit with a request to indicate whether or not a case had been seen in the previous month. Those notifying a case were sent a two‐page questionnaire. The main outcome measures were incidence of VKDB of early (first day of life), classic (days 2–7) and late‐onset (day 8 to 6 months) type; related morbidity and mortality; receipt of vitamin K; and predisposing factors. Results: Response rate of return of surveillance cards was high, averaging 94.5%. There were 35 notifications of which 23 were valid cases. Seventeen cases met criteria for confirmed VKDB, two for ‘probable’ and four for ‘possible’. There were eight confirmed classic cases with an overall incidence of 1.24 (95% confidence interval 0.54–2.45) per 100 000 births; none had received vitamin K prophylaxis, seven were fully breastfed and all fully recovered. There were nine confirmed late‐onset cases with an overall incidence of 1.40 (95% confidence interval 0.64–2.65) per 100 000 births; eight had received no vitamin K, eight were fully breastfed, six had liver disease, four suffered an intracranial haemorrhage and one died. Conclusions: In New Zealand, VKDB is virtually confined to fully breastfed infants not given vitamin K at birth. Late‐onset cases were frequently associated with liver disease.     

The effect of formula versus breast feeding and exogenous vitamin K1 supplementation on circulating levels of vitamin K1 and vitamin K-dependent clotting factors in newborns

The influence of breast or formula feeding together with that of a single supplementation of vitamin K₁ at birth, on the vitamin K₁ level and vitamin K-dependent clotting factors were studied in 65 breast and 15 formula fed infants. All breast fed newborns without supplementation (n=25) had very low serum vitamin K₁ at weeks 1 and 6. Oral vitamin K supplementation (n=22) or i.m. (n=18) at birth resulted in high serum levels at week 1, while at week 6 the effect had disappeared. Formula fed infants had vitamin K₁ values within the normal adult range at all study points. The low serum levels of vitamin K₁ were not associated with haemorrhagic disorders or coagulation abnormalities. The mean values of vitamin K₁ in maternal sera at weeks 1 and 6 were 2.3 nmol/l and 1.8 nmol/l and in breast milk 2.7 nmol/l and 2.0 nmol/l respectively. No correlation existed between the values in breast milk and maternal serum. To maintain serum levels of vitamin K₁ within the adult physiological range, repeated administration of low doses is needed in breast fed newborns beyond 1 week of age.     

Neonatal vitamin K prophylaxis in Denmark: three years' experience with oral administration during the first three months of life compared with one oral administration at birth

A Danish surveillance group established after the introduction of oral vitamin K prophylaxis monitored Danish cases with late onset vitamin K deficiency bleeding by regular questionnaires to all paediatric departments. Six cases were reported, one of whom died and three are severely handicapped. All cases occurred among an estimated 134,500 infants given a single oral 1 mg vitamin K' dose at birth. No cases have been reported so far during the existent regimen: 2 mg at birth and 1 mg weekly orally administered vitamin K during the first 3 months of life, given to at least 163,000 infants. The present study is concordant with the only other study on weekly peroral prophylaxis published. We consider the mentioned weekly regimen safe and appropriate.     

Prevention of vitamin K deficiency bleeding with oral mixed micellar phylloquinone: results of a 6-year surveillance in Switzerland

In 1995, a new form of vitamin K prophylaxis with two oral doses of 2 mg mixed micellar phylloquinone (Konakion MM) on the 1st and 4th day of life was introduced in Switzerland. It was hoped that this new galenic preparation of phylloquinone would protect infants with insufficient or absent bile acid excretion from late vitamin K deficiency bleeding (VKDB). Subsequently, the occurrence of VKDB was monitored prospectively between July 1, 1995 and June 30, 2001 with the help of the Swiss Paediatric Surveillance Unit (SPSU). Over a period of 6 years (475,000 deliveries), there were no cases of early (<24 h of age), one case of classical (2–7 days of life), and 18 cases of late (1–12 weeks) VKDB fulfilling standard case definitions. In 13/18 patients with late VKDB there was pre-existing liver disease and in 4/18 patients, parents had refused prophylaxis. The incidence of late VKDB for infants with completed Konakion MM prophylaxis was 2.31/100,000 (95% CI: 1.16–4.14) and for the entire population 3.79/100,000 (95% CI: 2.24–5.98). There was only one case of late VKDB after complete prophylaxis in an infant without underlying liver disease. Conclusion: two oral doses of 2 mg of a mixed micellar vitamin K preparation failed to abolish VKDB. The recommendations for vitamin K prophylaxis in Switzerland have therefore been changed to include a third dose at 4 weeks of age. Starting on January 1, 2004, the incidence of vitamin K deficiency bleeding will again be monitored prospectively by the Swiss Paediatric Surveillance Unit.Abbreviations CI confidence interval - SPSU Swiss Paediatric Surveillance Unit - VKDB vitamin K deficiency bleeding     

Assessing the population impact of low rates of breast feeding on asthma, coeliac disease and obesity: the use of a new statistical method

Background

Lack of breast feeding has been reported to be associated with a number of chronic childhood disorders.

Aim

To use a recently described measure, the population impact number of eliminating a risk factor over a time period (PIN‐ER‐t), to quantify the burden of low rates of breast feeding in a UK population of babies born in 2002 with regard to asthma, coeliac disease and obesity.

Methods

We performed literature searches for systematic reviews with meta‐analyses that had investigated the association between breast feeding and asthma, coeliac disease and obesity. Based on these data, and published data on the prevalence of breast feeding and the prevalence of the disorders, we calculated PIN‐ER‐t and estimated the number of cases of each disorder which could be prevented by eliminating “no breast feeding” as a risk factor.

Results

In the population of the 596 122 babies born in England and Wales in 2002, the number of cases of asthma, coeliac disease and obesity that could be prevented over 7–9 years if “no breast feeding” as a risk factor was eliminated were 33 100 (95% CI 17 710 to 47 543), 2655 (95% CI 1937 to 3343) and 13639 (95% CI 7838 to 19308), respectively.

Conclusions

The population burden of low breast feeding rates is high with regard to these chronic disorders. The use of PIN‐ER‐t allows the population burden of low breast feeding rates to be quantified and communicated in a way that will make it easier for both the general public and decision makers to understand.     

Implementing a Care Pathway for small and nutritionally at‐risk infants under six months of age: A multi‐country stakeholder consultation

Nutritional vulnerability under the age of 6 months is prevalent in low‐ and middle‐income countries with 20.1% infants underweight, 21.3% wasted and 17.6% stunted in a recent review. A novel Care Pathway for improved management of small and nutritionally at‐risk infants under 6 months and their mothers (MAMI) has recently been developed to provide outpatient care at large coverage. We aimed to investigate stakeholders’ views on the feasibility of its implementation and to identify barriers and enablers. This was an early stage formative mixed‐methods study: an online survey plus in‐depth interviews with country‐level stakeholders in nutrition and child health from different geographical regions and stakeholder groups. 189 stakeholders from 42 countries responded to the online survey and 14 remote interviews were conducted. Participants expressed an urgent need for improved detection and care for small and nutritionally at‐risk infants under 6 months. Whilst they considered the MAMI Care Pathway feasible and relevant, they noted it was largely unknown in their country. The most mentioned implementation barriers were: community‐specific needs and health care seeking barriers, health workers’ lack of competence in breastfeeding counselling and the absence of a validated anthropometric screening method. Possible enablers for its implementation were: patients’ preference for outpatient care, integrating the MAMI care pathway into existing maternal and child health programmes and the possibility of a local pilot project. Adaptation to the local context was considered crucial in further scale‐up.     

After their wives have delivered,a lot of men like going out: Perceptions of HIV transmission risk and support for HIV prevention methods during breastfeeding in sub‐Saharan Africa

Female‐initiated HIV prevention methods, such as oral pre‐exposure prophylaxis (PrEP) and the vaginal ring, may be important risk reduction strategies for breastfeeding women. Given their novelty, information about the sociocultural context and how it influences perceptions of and support for their use during breastfeeding is lacking. To address this gap, we conducted 23 focus group discussions separately with pregnant and breastfeeding women, male partners and grandmothers (N = 196) and 36 in‐depth interviews with key informants in Malawi, South Africa, Uganda and Zimbabwe. We analysed the data using a framework analysis method. Overall, breastfeeding was the norm, and participants described the transference of health (e.g., nutrition) and disease (e.g., HIV) to children through breast milk. Participants considered the early breastfeeding period as one of high HIV transmission risk for women. They explained that male partners tend to seek outside sexual partners during this period because women need time to recover from delivery, women focus their attention on the child, and some men are disgusted by breast milk. Participants highlighted concerns about the drugs in oral PrEP transferring to the child through breast milk, but fewer worried about the effects of the vaginal ring because the drug is localized. Women, grandmothers and key informants were supportive of women using these HIV prevention methods during breastfeeding, while male partners had mixed opinions. These findings can be used to tailor messages for promoting the use of PrEP or the vaginal ring during breastfeeding in sub‐Saharan Africa.     

高危因素对早产儿发育的影响及其干预效果

目的 探讨高危因素对早产儿营养、智能、神经发育的影响及干预效果.方法 选择2008年1 ～12月在我院出生并定期在儿童保健科进行体格检查的早产儿,根据是否伴有高危因素(超早产、极低出生体重、脑损伤、高胆红素血症、重度窒息)分为高危因素组和非高危因素组.高危因素组再根据家长干预依从性分成干预组和非干预组,同时匹配本院足月分娩的健康婴幼儿为足月儿组.比较不同组别校正年龄2岁时的营养、智能和神经发育结局以及干预效果.结果 完成随访早产儿372例,其中非高危因素组223例,高危因素组149例(干预组71例,非干预组78例),足月儿组231例.不同组别婴幼儿性别、分娩方式、家庭经济水平,以及干预组与非干预组基础疾病差异均无统计学意义(P＞0.05).校正年龄2岁时,高危因素组贫血和维生素D缺乏发生率高于非高危因素组(15.4％比6.7％,19.5％比11.2％),非干预组高于干预组(23.1％比7.0％,25.6％比12.7％),早产儿组、高危因素组和非干预组发育商(DQ,分)均低于相应的足月儿组、非高危因素组和干预组[(85.2±11.4)比(98.3±5.3),(79.5±13.4)比(89.0±7.8),(71.2±10.9)比(88.6 ±9.4)],智能低下和脑性瘫痪发生率均高于相对应的足月儿组、非高危因素组和干预组(智能低下:7.0％比0.4％,16.8％比0.5％,30.8％比1.4％,脑性瘫痪:3.0％比0.4％,6.0％比0.9％,10.3％比1.4％),差异均有统计学意义(P＜0.05).结论 2岁内早产儿发育落后于足月儿,高危因素增加早产儿营养不良、DQ低下和脑性瘫痪的风险,而干预能一定程度改善早产儿发育.     

Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies

Background

Coeliac disease (CD) is a disorder that may depend on genetic, immunological, and environmental factors. Recent observational studies suggest that breast feeding may prevent the development of CD.

Aim

To evaluate articles that compared effects of breast feeding on risk of CD.

Methods

Systematic review and meta‐analysis of observational studies published between 1966 and June 2004 that examined the association between breast feeding and the development of CD.

Results

Six case‐control studies met the inclusion criteria. With the exception of one small study, all the included studies found an association between increasing duration of breast feeding and decreased risk of developing CD. Meta‐analysis showed that the risk of CD was significantly reduced in infants who were breast feeding at the time of gluten introduction (pooled odds ratio 0.48, 95% CI 0.40 to 0.59) compared with infants who were not breast feeding during this period.

Conclusions

Breast feeding may offer protection against the development of CD. Breast feeding during the introduction of dietary gluten, and increasing duration of breast feeding were associated with reduced risk of developing CD. It is, however, not clear from the primary studies whether breast feeding delays the onset of symptoms or provides a permanent protection against the disease. Long term prospective cohort studies are required to investigate further the relation between breast feeding and CD.     

Association between early initiation of breastfeeding and reduced risk of respiratory infection: Implications for nonseparation of infant and mother in the COVID‐19 context

Early initiation of breastfeeding, within 1 h of birth, is vital for the health of newborns and reduces morbidity and mortality. Secondary analysis of the 2016 Nepal Demographic and Health Survey (DHS) showed that early initiation of breastfeeding significantly reduced the risk of acute respiratory infection (ARI) in children under 2 years. Early initiation of breastfeeding requires maternal proximity. Separation of infant and mother inhibits early initiation of breastfeeding and increases the risk that infants will suffer from ARIs. However, during the COVID‐19 pandemic, guidance varied, with some recommending that infants and mothers with SARS‐CoV‐2 be isolated from one another. Nepal''s Ministry of Health and Population recommended nonseparation, but the adherence to this guidance was inconsistent. Maternal proximity, nonseparation and early initiation of breastfeeding should be promoted in all birthing facilities.     

早产儿脐血维生素K依赖因子水平及产前补充维生素K1对其影响的研究

目的了解早产儿是否存在维生素(Vit)K依赖因子水平低下及其与早产儿脑室周围-脑室内出血的关系,探讨产前补充维生素(Vit)K1对早产儿血浆VitK依赖因子水平的影响及对脑室周围-脑室内出血的预防作用.方法将有早产可能且至分娩时孕周不足35周的孕妇分为两组对照组133例,在产前给予地塞米松注射;对照组44例,产前给予地塞米松+VitK1.两组早产儿各30例留取脐动脉血离心零下20℃以下保存用凝固法检测Ⅱ、Ⅶ、Ⅸ、Ⅹ等凝血因子活性水平,同时留取同期出生的健康足月新生儿30例脐血标本作对照.两组早产儿生后1周内常规作头颅超声检查以明确有无脑室周围-脑室内出血及其程度.结果早产儿与足月新生儿脐血VitK依赖因子活性水平分别为Ⅱ(25.6±9.5)%对(36.7±4.9)%,Ⅶ(59.0±17.7)%对(64.5±10.6)%,Ⅸ(24.7±8.9)%对(30.2±5.7)%,Ⅹ(30.2±5.0)%对(34.3±12.6)(P<0.05).母亲产前补充VitK1后其婴儿脐血VitK依赖因子水平分别为Ⅱ(36.4±6.9)%,Ⅶ(69.6±16.6)%,Ⅸ(25.7±10.9)%和Ⅹ(39.3±8.0)%,除Ⅸ因子外,Ⅱ、Ⅶ和Ⅹ因子活性均显著升高(P<0.05).脑室周围-脑室内出血发生率在对照组为52.6%,观察组为31.8%(χ2=5.744,P=0.017);重度出血对照组为12.0%,观察组为2.3%(χ2=3.626,P=0.057).结论早产儿存在VitK依赖因子水平低下,可能为其易于发生脑室周围-脑室内出血的原因之一.分娩前母亲补充VitK1可显著提高其血浆Ⅱ、Ⅶ和Ⅹ因子水平,并对脑室周围-脑室内出血有一定的预防作用.     

Effect of exclusive breast‐feeding and early solid food avoidance on the incidence of atopic dermatitis in high‐risk infants at 1 year of age

The aim of this study was to assess the preventive effect of exclusive breast‐feeding and early solid food avoidance on atopic dermatitis (AD) in infancy. This study is part of a dietary clinical trial in a prospective cohort of healthy term newborns at risk of atopy. It was recommended to breast‐feed for at least 4 months and to avoid solid food in the same time‐period. Eight hundred and sixty‐five infants exclusively breast‐fed, and 256 infants partially or exclusively formula‐fed, were followed‐up until the end of the first year following birth. AD and sensitization to milk and egg were considered as study end‐points. The 1‐year incidence of AD was compared between the two study groups. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. The incidence of AD was calculated in relation to age at introduction of solid food and amount of food given. In the breast‐fed group, the adjusted OR for AD was 0.47 (95% CI 0.30–0.74). The strongest risk factor was the occurrence of AD in the subject's core family. The risk of infants with AD to be sensitized to milk was four times higher, and to egg eight times higher, than in infants without AD. Age at first introduction of solid food and diversity of solid food showed no effect on AD incidence. We conclude that in infants at atopic risk, exclusive breast‐feeding for at least 4 months is effective in preventing AD in the first year of life.