Current 26.9

1. Obstetrics, Gynaecology and Reproductive Medicine Obstetrics, Gynaecology and Reproductive Medicine is a great revision guide for the MRCOG and beyond. Obstetrics, Gynaecology and Reproductive Medicine is an authoritative and comprehensive resource that provides all obstetricians, gynaecologists and specialists in reproductive medicine with ready access to up-to-date information on all aspects of obstetrics and gynaecology. Over a three-year cycle of 36 issues, the emphasis of the journal is on the clear and concise presentation of information of direct clinical relevance to specialists in the field and candidates studying for MRCOG Part II. Each volume contains review articles on obstetric and gynaecological topics. The journal is invaluable for specialists in obstetrics and gynaecology, both in their role as trainers of MRCOG candidates and in keeping up to date across the broad span of the subject area. Over any three-year period, a subscription will ensure access to up-to-date, understandable information on the full range of obstetrics, gynaecology and reproductive medicine topics. Editor-in-Chief Alec McEwan BA BM BCh MD MRCOG Consultant in Fetal and Maternal Medicine, Department of Obstetrics and Gynaecology, Queen’s Medical Centre, Nottingham, UK Associate Editors Sabaratnam Arulkumaran MBBS MD PhD FRCS (Ed) FRCOG Professor of Obstetrics and Gynaecology, Department of Obstetrics and Gynaecology, St. George’s Hospital Medical School, London, UK Tahir A Mahmood MD FRCOG FRCPI MBA FACOG(Hon) Consultant Obstetrician and Gynaecologist, Victoria Hospital, Kirkcaldy, Fife, UK Philip N Baker FRCOG, FMedSci Pro-Vice-Chancellor and Head of the College of Medicine, Biological Sciences and Psychology, Dean of the School of Medicine, University of Leicester, UK Fiona Reid MD MRCOG Consultant Urogynaecologist, St Mary’s Hospital, Manchester, UK Shreelata Datta BSc(Hons) MBBS MRCOG LLM Consultant Obstetrician and Gynaecologist, King’s College Hospital, London, UK Mahmood I Shafi MB BCh MD DA FRCOG Consultant Gynaecological Surgeon and Oncologist, Addenbrooke’s Hospital, Cambridge, UK Trainee Editor Catherine Aiken MB/BChir MA PhD MRCP MRCOG Specialist Registrar (ST5) and Academic Clinical Lecturer in Obstetrics and Gynaecology, Addenbrooke’s Hospital, Cambridge, UK Obstetrics, Gynaecology and Reproductive Medicine has an eminent editorial board, all of whom are recognized experts in their field. Visit our website at: www.obstetrics-gynaecology-journal.com for previous issues, subscription information and further details.

2. Non-HIV sexually transmitted infections in pregnancy Annette Thwaites Helen Iveson Shreelata Datta Eleanor Draeger Abstract Sexually transmitted infections (STIs) are common, especially in young women, and pregnant women are inherently at risk. In pregnancy, sexually transmitted infections can have serious consequences for the woman, the fetus and neonate yet may remain asymptomatic throughout. Screening for many STIs is not explicit in UK antenatal guidelines and may be overlooked. Therefore it is essential to consider a woman’s risk of STIs regularly throughout pregnancy and know how and when to undertake an appropriate sexual history and relevant testing. Early diagnosis and treatment, partner notification and multidisciplinary management together with genitourinary physicians and paediatricians are key to securing good outcomes for mother and child. This article reviews the presentation, diagnosis and management of non-HIV STIs in pregnancy, highlighting indications for testing and important differences compared with management of non-pregnant women. Keywords chlamydia; gonorrhoea; pregnancy; sexually transmitted infections; syphilis Introduction Sexually transmitted infections (STIs) have a heterogeneous distribution and are increasing in prevalence nationally and globally. The World Health Organisation (WHO) 2008 figures estimate the following numbers of new cases and global prevalence: Trichomoniasis vaginalis (276.4 million, 7.8%), Chla- mydia trachomatis (105.7 million, 3%), Neisseria gonorrhoeae (106.1 million, 3%) and Syphilis (10.6 million, 0.3%). The UK national survey of sexual attitudes and lifestyles 2013 (Natsal) undertook urine testing for chlamydia and gonorrhoea among participants and revealed a prevalence of 1.5% and <0.1% respectively among women of all ages. These rose to 4.7% and 0.2% in under 25 age groups. Many STIs can be asymptomatic and yet in pregnancy can have catastrophic consequences for the woman and fetus. Ascending infection in pregnancy can lead to chorioamnionitis and subsequent premature rupture of membranes, preterm delivery, low birth weight and maternal sepsis. Fetal infection can arise via transplacental, intrapartum or postpartum transmission. Initial screening for HIV, syphilis and hepatitis B and C are part of routine antenatal blood tests, taken ideally before 10 weeks, as recommended by NICE guidance. However diagnosis of more common STIs such as chlamydia or herpes rely on women self-screening, presenting with symptoms or on history alone. Therefore clinicians must retain a high index of suspicion for STIs throughout antenatal and postnatal care. Risk factors for STIs include age under 25, high number of sexual partners and any new sexual partners in pregnancy, diagnosis of any other STI, country of origin with high prevalence, intravenous drug use, and commercial sex. A careful sexual history should be taken at the start of pregnancy to establish a woman’s risk and identify any high risk partners, such as those with known or suspected STIs or men who have sex with men (MSM). This should be revisited regularly and used to initiate further screening tests as appropriate (Table 1). The key principles to successfully managing STIs in pregnancy are early diagnosis and effective treatment together with minimising the risk of re-infection and vertical transmission. Partner notification and treatment, abstinence during and post treatment and risk reduction are important and common to the management of all STIs. Management in pregnancy may differ depending on gestation, stage of infection and contraindication to drugs and test of cure (TOC) is often advised. Mode of delivery is not commonly influenced by the presence of an STI with the exception of herpes. Neonatal management may be determined on mode of delivery and the condition of the baby. Multidisci- plinary working with genitourinary physicians and paediatricians is therefore vital to optimising outcomes for the mother and child. Chlamydia Genital chlamydia infection is caused by the obligate intracellular pathogen Chlamydia trachomatis and is the most common bacterial STI in the UK with a peak of almost 1 in 20 women infected in the 18e19 age group. The cervix is the most commonly infected site in women but the urethra, throat and rectum may also be infected. Concurrent infection of urogenital and anorectal sites are estimated up to 77% but there is scarce data as to rates of pharyngeal infection in women. 85% of women are asymptomatic although may present with postcoital bleeding, lower abdominal pain, purulent vaginal discharge, cervicitis, proctitis or dysuria. Untreated, Chlamydia can persist for years leading to a wide range of complications including pelvic inflammatory disease (PID), ectopic pregnancy, tubal factor infertility and chronic pain. Annette Thwaites MEng MA (Cantab) MSc MB BChir DFSRH is an ST2 in Community Sexual and Reproductive Health at University Hospital Lewisham, London, UK. Conflicts of interest: none declared. Helen Iveson MBBS BSc MRCP DipGUM DipHIV DFSRH PGA Med Ed is a Locum Consultant in Genitourinary Medicine at Guy’s and St Thomas’ Hospital, London, UK. Conflicts of interest: none declared. Shreelata Datta MBBS BSc (Hons) LLM MRCOG is a Consultant Obstetrician and Gynaecologist at King’s College Hospital, London, UK. Conflicts of interest: none declared. Eleanor Draeger MBBS MA (Oxon) DFSRH MRCP DipGUM DipHIV is a Consultant in Genitourinary Medicine at University Hospital Lewisham, London, UK. Conflicts of interest: none declared. REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 253 Ó 2016 Elsevier Ltd. All rights reserved.

3. STI testing STI Test When to test Chlamydia C Nucleic Acid Amplification Test (NAAT) C vulvovaginal or endocervical swabs (clini- cian or self-taken) C Pharyngeal or rectal swabs if sexual history indicates C Window period typically 2 weeks C At booking appointment in under 25s C If any new sexual partner C Regularly if any high risk partner C Diagnosis of another STI C If symptomatic (focal or signs of sepsis) C After 6 weeks post treatment with azithromycin C After 5 weeks post treatment with alternative regimens C In 3rd Trimester if tested positive earlier in pregnancy C Neonatal conjunctivitis or pneumonia Gonorrhoea C NAAT C vulvovaginal or endocervical swabs (clini- cian or self-taken) C Confirmatory culture and sensitivities C Pharyngeal or rectal swabs if sexual history indicates C Window period typically 2 weeks C At booking appointment in under 25s C If any new sexual partner C Regularly if any high risk partner C Diagnosis of another STI C If symptomatic (focal or signs of sepsis) C After 72 hours post treatment if symptoms persist C After 2 weeks post treatment if asymptomatic C In 3rd Trimester if tested positive earlier in pregnancy C Neonatal conjunctivitis or neonatal sepsis Trichomoniasis C Microscopy of vaginal secretions from posterior fornix mixed with saline and culture C May find on high vaginal self-taken swab C NAAT more sensitive and becoming increasingly available C Regularly if any high risk partner C Diagnosis of another STI C vaginal discharge or vulvitis Syphilis C IgM and IgG serology C Dark Ground microscopy C Cardiolipin RPR/VDRL test to monitor response to treatment C Polymerase Chain reaction (PCR) limited availability C At booking appointment C Any genital ulceration C If any new sexual partner C Diagnosis of another STI C Repeat testing at 6 weeks and 3 months if high risk exposure or ulceration and initial testing negative Genital Warts C Clinical diagnosis Genital Herpes C PCR of vesicle fluid on viral swab C Herpes Simplex Virus (HSV) type specific antibody test C Any genital ulceration C Suspected/known HSV positive partner C Genital ulceration in 3rd Trimester Hepatitis A,B,C C Serology C High risk groups (Sex workers, sexual as- sault, anal sex, oro-anal sex and sexual acts likely to break mucosal barrier) C Prodromal or icteric symptoms or signs of chronic liver disease HIV C HIV antibody AND p24 antigen blood test C Window period typically 4e5 weeks C At booking appointment C Any new sexual partner C Regularly if high risk partner C Diagnosis of another STI and retest 4 weeks after last episode of sex without condom use Table 1 REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 254 Ó 2016 Elsevier Ltd. All rights reserved.

4. In pregnancy, chlamydia infection can spread from the cervix into the uterine cavity causing chorioamnionitis and subsequent premature rupture of membranes, preterm delivery, low birth weight and maternal sepsis. It is unknown if the risks differ between primary infection or persistent or recurrent infection but there is some evidence to suggest that risks of complications are increased if infection occurs at earlier gestations. Perinatal transmission can also occur with infected babies typically presenting with conjunctivitis, pneumonia or otitis media. Approx- imately 50% of neonates born to women with untreated Chlamydia will develop ophthalmia neonatorum and 15% pneumonitis. Current NICE guidance on antenatal care recommends informing under 25s at their booking appointment, and ideally before 10 weeks, about the high prevalence of Chlamydia in their age group and give details of local screening. However the national chlamydia screening programme, in contrast to other national screening programmes, relies on patients self-presenting. Therefore if a patient is high risk and unlikely to access testing successfully in the community, testing at booking and regularly in each trimester of pregnancy is advisable. First line treatment, as recommended by the US Center for Disease Control and Prevention (CDC) 2015 guidelines, is with 1g azithromycin orally, as for non-pregnant women. This has been widely used with good safety data, however is unlicensed for use in pregnancy in the UK and the BNF states that manufacturers advise use only if adequate alternatives are unavailable. How- ever, doxycycline and ofloxacin are contraindicated in pregnancy and therefore alternative treatment is limited to erythromycin or amoxicillin of varying regimens over 7e14 days. Azithromycin is preferred on the basis of better compliance and side effect profile. Management must also include partner notification and treatment and advice to avoid all sex (including oral sex and sex with a condom) until a week after completion of treatment and avoidance of all sex with current partners until a week after they have also finished treatment. Due to higher positive chlamydia tests after treatment in pregnancy resulting from either reduced efficacy of treatment in pregnancy, non-compliance or re-infection, TOC is recommended. Current UK guidelines recommend this should be performed no earlier than 3 weeks after completing treatment as residual, non-viable, chlamydial DNA may be detected for 3e5 weeks after treatment. TOC is not routinely recommended in non-pregnant women. Gonorrhoea The causative organism is the gram negative intracellular diplo- coccus bacterium Neisseria gonorrhoeae. Infection, whilst still relatively uncommon in the general UK population, is still significant among those with other risk factors such as co-infection and is more prevalent in the under 25s living in urban, deprived areas. Public Health England figures also show that the diagnoses of gonorrhoea between 2013 and 2014 revealed a large proportional increase of 19%. As for Chlamydia, the primary site of infection is most commonly the endocervix but, can also be the mucous membranes of the urethra, rectum, pharynx and con- junctiva. Genital gonorrhoea infection can produce the same symptoms as Chlamydia and, whilst more often symptomatic than Chlamydia, Gonorrhoea is still asymptomatic in up to 50% of cases. Without treatment Gonorrhoea can also cause PID with associated longer term complications and haematogenous dissemination, although uncommon, may also occur causing skin lesions, arthralgia, arthritis and tenosynovitis. As with Chlamydia, there are important consequences in pregnancy which can be severe. Infection can ascend similarly causing chorioamnionitis, premature rupture of membranes, preterm delivery, low birth weight and postpartum infection. There is some recent evidence that infection diagnosed in the first trimester of pregnancy increases the likelihood of preterm birth. Neisseria gonorrhoeae is also transmitted to the neonate in 30 e50% of cases. This occurs during delivery or, less commonly and in the context of prolonged rupture of membranes, before birth. The most common presentation is gonococcal ophthalmia neonatorum with profuse purulent conjunctival discharge of the newborn. This invariably causes blindness if untreated and so the neonate should receive prophylactic erythromycin ophthalmic ointment at birth regardless of mode of delivery. Current UK guidance on recommended management was changed in 2011 driven by recognition of increasing resistance of Neisseria gonorrhoeae to multiple antibiotics. First-line treatment is now ceftriaxone 500 mg intramuscularly (IM) plus azithromycin 1g orally. This regimen is for treatment of both pregnant and non-pregnant women with a second line alternative of 2g Spectinomycin plus azithromycin 1g orally in pregnancy. Azithromycin is effective against the high rates of co-infection with Chlamydia but the dual therapy has been adopted primar- ily to delay the onset of widespread cephalosporin resistance as the development of simultaneous resistance to two different antimicrobial classes is thought less likely. Partner notification, treatment and advice on abstinence is as for chlamydial infection. However TOC is recommended in all cases, within and outside of pregnancy, reflecting emergence of resistance to treatment. This should be carried out at 72 hours after completion of treatment if the woman remains symptomatic and at 2 weeks if asymptomatic. Trichomoniasis Infection with Trichomonas Vaginalis (TV), a flagellated proto- zoon, is the commonest non-viral STI worldwide with incidence of 248 million new cases per year. The prevalence is higher in tropical countries with a staggering 20% prevalence in the Afri- can and Americas WHO regions. In the UK there were only around 6000 diagnoses in 2014 mainly among women with highest rates seen in London among black Caribbean ethnic groups and in those with another concurrent STI. Unlike most other STIs, prevalence is not highest in the younger age groups. In women, the organism can be found in the vagina, urethra and paraurethral glands with vaginal infection almost always spreading to the urethra but sole urethral infection presenting less than 5% of cases. While in men the infection is usually asymptomatic and therefore far less diagnosed, infection is women is asymptomatic in less than half of cases. Common symptoms include offensive vaginal discharge (classically purulent green or frothy yellow), vulvo-vaginitis (associated with itching or dysuria) but infection can also cause pelvic pain or vulval ulceration. A small minority of women will also have a REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 255 Ó 2016 Elsevier Ltd. All rights reserved.

5. “strawberry” cervix on speculum examination describing the appearance of punctate haemorrhages. Whilst there is increasing evidence that TV infection is associated with preterm delivery, low birth weight and maternal postpartum sepsis, further research is needed before a causal link is established. There are also studies that suggest infection with TV may increase HIV acquisition and transmission. There is no existing evidence to suggest additional neonatal effects or puerperal infection. Further research is also needed to inform the management of TV in pregnancy as studies to date have shown little impact of treatment regimens on pregnancy outcomes. A spontaneous cure rate is approximately 20e25%. However, current treatment with metronidazole is currently advised at all stages of pregnancy with a cure rate of over 90%. Historical concerns regarding teratogenicity, as metronidazole readily crosses the placenta, have not been supported by more recent meta-analyses. The BNF advises against high dose regimens so 400e500 mg twice daily for 5e7 days is usual and may be associated with fewer side effects compared to a single dose. Women who drink alcohol in pregnancy should be advised not to do so for the duration and at least 48 hours after treatment because of the possibility of a disulfiram-like reaction. Tinidazole, used as an alternative treatment outside of pregnancy is contraindicated in the first trimester and its safety in later pregnancy has also not been well-evaluated. If an alternative to metronidazole is needed, close liaison with GUM and allergy teams is necessary. Any sexual partners within the 4 weeks prior to presentation should be treated simultaneously and patients should be advised to avoid sex for a week after they and their partners have completed treatment. TOC is recommended if the patient remains symptomatic following treatment or if symptoms recur but may be carried out in pregnancy. Syphilis Syphilis is caused by infection with the spirochete bacterium Treponema pallidum. Whilst still relatively rare in the UK with only 265 cases diagnosed in women in 2012, prevalence has been rising steeply, with the highest proportional increase of all STI diagnoses in 2013 (33%). Syphilis is transmitted by sexual contact with an infectious lesion or vertical transmission. Acquired syphilis is categorized into early (primary, secondary and early latent) and late (late latent or tertiary) phases. Late syphilis is not usually infectious to sexual partners. Signs of infection can vary enormously between individuals and stage of infection and it has been known as “the great imitator” due to its frequent atypical presentations resembling other conditions. Primary syphilis classically presents with a single, painless anogenital ulcer or “chancre” with inguinal lymphadenopathy. However, any ulcer in this area should be considered to be syphilis until proven otherwise. Secondary syphilis is multisystem involvement within 2 years of infection and often presents with rash (typically non-itchy, macular- papular affecting the palms and soles), condylomata lata and generalized lymphadenopathy but also less commonly with patchy alopecia, anterior uveitis, meningitis, cranial nerve palsies, hepatitis, splenomegaly, periostitis and glomerulone- phritis. The latent phase is asymptomatic and split between “early”, i.e. less than 2 years from infection and “late” thereafter. Symptomatic late syphilis includes neurosyphilis, cardiovascular and gummatous forms and it has been estimated that, without antibiotic treatment, approximately one third of cases progress to this stage within 15 years of infection. In pregnancy, syphilis can be transmitted transplacentally at any stage leading to polyhydramnios, miscarriage, preterm labour, stillbirth, hydrops and congenital syphilis. Vertical transmission causes high infant mortality and morbidity worldwide but UK rates are low due to antenatal screening, recommended at booking within the first 10 weeks. Maternal early syphilis and high RPR/VDRL titres are risk factors for congenital syphilis but transmission can also occur in late latent maternal infection. HIV co-infection may also increase transmission risk. Referral should be made to fetal medicine for repeat ultrasound evaluation, usually at 20, 28 and 36 weeks gestation. Many infected neonates are asymptomatic at birth but may present with rash, hep- atosplenomegaly, syphilitic snuffles and periostitis. Signs of late syphilis in infants include keratitis, Hutchinson’s incisors, Moon’s mulberry molars, saddlenose deformity, frontal bossing and deafness. Treatment of early syphilis is usually with single dose Ben- zathine penicillin 2.4MU IM. However concentrations may be reduced by the physiological changes of pregnancy and so treatment in the last trimester, which is associated with poorer outcomes, should include a second dose a week after. Three doses are given weekly for late syphilis in pregnancy. Re- treatment is advised if syphilis has previously been diagnosed and there is uncertainty over previous treatment, if RPR/VDRL titres have not demonstrated four-fold drop or remains higher than 1:8. Procaine penicillin can also be used but non-penicillin alternatives such as ceftriaxone or macrolides have not been well or favourably evaluated and so skin testing and desensiti- zation should be considered in patients with a history of penicillin allergy. Maternal and fetal monitoring during treatment after 26 weeks gestation is necessary due to potential Jarisch eHerxheimer and anaphylactic reactions. JarischeHerxheimer usually presents within 12 hours as an acute febrile illness with headache, myalgia and rigors, resolving within 24 hours. It is thought to be caused by the release of endotoxin-like substances when large numbers of Treponema pallidum are killed and occurs in approximately 40% of cases in pregnancy. This reaction may provoke uterine contractions and fetal heart rate de- celerations and therefore a theoretical increased risk of preterm delivery and fetal demise. This should be managed supportively with antipyretics and there is no evidence for steroid therapy although this has been used. Follow up should include repeat serology to monitor treatment response, re-infection and relapse and is indicated for more than 12 months at a frequency guided by VDRL/RPR levels. Sexual partners must also be tested and partner notification should extend to 3 months for primary syphilis and 2 years for secondary syphilis. Any previous serology is therefore helpful to stage the disease and inform partner notification, particularly in latency and should be pursued together with sexual health col- leagues. Careful paediatric assessment, serial serological testing and consideration of neonatal treatment are also required post- delivery. Treatment for congenital syphilis is indicated based on clinical suspicion, absence or inadequate maternal treatment, REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 256 Ó 2016 Elsevier Ltd. All rights reserved.

6. non-penicillin regimens or treatment less than 4 weeks prior to delivery. Older siblings should also be screened for congenital syphilis. Genital warts Genital warts are extremely common worldwide and are most commonly caused by the human papillomavirus (HPV) subtypes 6 and 11, with a small minority due to other subtypes. It is estimated that approximately 70% of all those sexually active have been exposed to the virus. The virus is spread by genital skin-to-skin contact and transmission can occur from partners without visible warts due to asymptomatic viral shedding. The incubation period is on average 3 months but can be much longer and therefore it is often impossible and unhelpful to identify the source of infection. The diagnosis is clinical with typical lesions evident as single or multiple, fleshy, cauliflowerelike lumps on the genital or perianal areas. Studies on HPV infection in pregnant women have produced inconsistent results but there is some evidence that prevalence may be as high as 65% with the majority cleared in pregnancy and low levels of new infections. Key risk factors for HPV acquisition and persistence of HPV infection include young age, smoking, other STIs and immunosuppressive conditions. It is anticipated that the prevalence of genital warts in pregnant women will decrease with the adoption of quadrivalent HPV vaccination which targets both high risk oncogenic subtypes and low risk subtypes 6 and 11. This was started in the UK in 2012. The vast majority of cases of genital warts cause no problems in pregnancy or labour. They can however enlarge rapidly in the second and third trimesters and are often more resistant to treatment. The management of genital warts is importantly different, with topical treatments such as podophyllotoxin contraindicated due to possible teratogenicity and imiquimod similarly unlicensed in pregnancy. Therefore active treatment in pregnancy should be limited to weekly cryotherapy and consideration of excision or deferred treatment if there is no improvement after 4 weeks. Warts often regress spontaneously postpartum. Vertical transmission can cause genital warts and laryngeal papillomatosis but is very rare. The prevalence of laryngeal papillomatosis has been estimated at 4.5 per 100,000 children. Treatment aims to minimize the number of lesions present at delivery to reduce the neonatal exposure to virus. However since the mechanisms of vertical transmission of HPV are poorly un- derstood and the complications are so rare, no treatment and vaginal delivery are considered safe. Caesarean section is only rarely indicated if the vaginal outlet or cervix are grossly obstructed with warts. Genital herpes Genital herpes is a common infection worldwide. It is caused by the herpes simplex virus (HSV) type 1 or type 2 and although most genital herpes globally is caused by type 2, in the UK and other developed countries the cause is equally likely to be either type. In 2013 there were approximately 20,000 new diagnoses of genital herpes in women in England. It is twice as common among women as men of the same age and the prevalence is greatest among 20e25 year olds with around 70% of under 25s in the UK already infected with HSV type 1 or 2. The virus is transmitted by skin-to-skin contact and can occur during vaginal, anal and oral sex, including sex with condoms. The incubation period is usually 5e14 days but can be longer so it is often difficult to ascertain the partner source of infection. The typical lesions of genital herpes are shallow, painful vesicles or ulcers of the genital or perianal area; however, many experience mild or no symptoms. Conversely patients may have systemic features such as malaise, myalgia, headache and lymphadenopathy. Patients may also present with isolated dysuria or constipation so genital examination should be undertaken, particularly in the context of pregnant women with culture negative or persistent “urinary tract infection”. Symptomatic episodes usually spontaneously resolve within 3 weeks. If genital lesions are present there is a high risk of passing on the virus to sexual partners but asymptomatic shedding and transmission also occurs, particularly in the first year after infection. The virus then lies dormant in a dorsal root ganglion and reactivates variably which may lead to recurrent symptomatic episodes, often preceded by a prodrome of localized tingling for a few days. The majority of women with genital herpes will have a recurrence during pregnancy and women can experience more outbreaks when pregnant. HSV-2 typically recurs more frequently than HSV-1. However, clinical diagnosis is neither sensitive nor specific and PCR testing of vesicle fluid and type- specific serological tests are required to distinguish between primary and recurrent infection which has major implications for management. Primary HSV can cause miscarriage, preterm delivery, low birth weight and neonatal herpes. Neonatal herpes is rare in the UK, occurring in 1e2 out of every 100,000 newborn babies, however, it is almost always symptomatic with high mortality. It is categorized as localized (to skin, eye or mouth), encephalitic or disseminated multi-organ infection. The majority of cases occur as a result of direct contact with maternal secretions at birth but postnatal infection also occurs due to contact with oral herpes. Congenital herpes by transplacental infection in utero is extremely rare. The risk of transmission is greatest when a woman acquires new infection in the third trimester, particularly within 6 weeks of delivery, as viral shedding may continue till delivery and the baby is unlikely to have protective transplacental maternal antibodies. Serological testing is required as up to 15% of women presenting with a first episode will actually be recurrence. Testing may be difficult to interpret and women should be referred to genitourinary physicians. However, since results may not be available for some time, primary infection should be assumed in the interim. Serological testing may also be useful in the context of a partner with suspected or known HSV to establish true discordance and advise on how to minimize transmission during pregnancy. The RCOG/BASHH guidance strongly recommends vaginal delivery for women with primary and recurrent genital herpes in the first or second trimesters with no other indications for caesarean section. Women should be reassured that there is no evidence that recurrent HSV infection is associated with miscarriage or congenital abnormalities. Whilst GUM referral should be made, this should not delay initiation of treatment, in line with clinical condition, to reduce the duration and severity of the episode. Aciclovir, although not licenced in pregnancy, has REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 257 Ó 2016 Elsevier Ltd. All rights reserved.

7. been used extensively without reported problems. From 36 weeks gestation, 400 mg three times daily aciclovir should be offered to prevent recurrence at term. This is increased from a twice daily prophylactic dose outside of pregnancy. There is limited data on the neonatal safety of prophylaxis so the risks and benefits should be discussed with women. In the final trimester vaginal delivery should also be recommended in recurrent cases as the risk of transmission remains low (0e4%), even if lesions are present at delivery. Invasive procedures may be used if necessary and in women with spontaneous rupture of membranes at term, most clinicians expedite delivery to minimize neonatal exposure. However in primary HSV infection in the third trimester, caesarean section is indicated as the neonatal transmission rate is as high as 41% within 6 weeks of expected delivery. Prophylactic aciclovir should commence and continue until delivery. If caesarean section is declined or vaginal delivery is unavoidable, intravenous aciclovir should be considered and invasive procedures avoided. Babies will need testing and specialist neonatal care with preterm babies most at risk of disseminated HSV infection. In the context of preterm prelabour rupture of membranes (PPROM) and HSV infection, there is limited evidence to guide management. However current expert opinion suggests that expectant management with oral aciclovir is appropriate for recurrent HSV and PPROM before 34 weeks gestation. After this time, the management is the same as without HSV. However, when PPROM is complicated by primary HSV infection, there is no evidence base for management and therefore a plan should involve a senior multidisciplinary team. Conservative management should include prophylactic intravenous aciclovir and caesarean section should be considered if delivery is indicated within 6 weeks of primary HSV infection. Hepatitides Viral hepatitis is caused by several very different viruses and is usually transmitted by the faecaleoral (Hepatitis A) or blood- borne routes (Hepatitis B and C). However they should be considered as potential STIs in the context of high risk groups including commercial sex workers, sex associated with drug and alcohol use, co-infection with HIV and other STIs, group sex and acts such as oro-anal sex or those which compromise the vaginal or rectal mucosa. Prodromal or icteric symptoms (loss of appetite, fatigue, abdominal pain, nausea and vomiting, fever, diarrhoea, dark urine and pale stools, jaundice and pruritus) should also prompt serological testing and patients should be warned of the increased risks of miscarriage, preterm labour and vertical transmission. The highest risk of vertical transmission is associated with maternal Hepatitis B and neonates should therefore be vaccinated at birth with IgG. Treatment in pregnancy is contro- versial and should involve a heptologist. Screening and vaccination of sexual partners may be indicated and abstinence advised until successful Anti-Hepatitis B surface antibody titres attained. Conclusion STIs in pregnancy represent a significant risk to the mother and child. Clinicians should consider the risks regularly throughout the pregnancy in order to test, diagnose and manage effectively. Treatment regimens often differ in pregnancy and multidisciplinary teams are needed. The impact on mode of delivery de- pends on the timing and type of infection in relation to pregnancy gestation. Referral to the fetal medicine team for ultrasound assessment of growth and structural abnormalities must be considered early. Test of cure, partner notification and treatment, risk reduction advice, testing for other STIs and retesting must not be overlooked. A FURTHER READING Sonnenberg Pam, Clifton Soazig, Beddows Simon, et al. Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal). Lancet November 2013; 382: 1795e806. Public Health England sexually transmitted infections and Chlamydia screening in England: 2014 Health Protection Report 9(22) https:// www.gov.uk/government/uploads/system/uploads/attachment_ data/file/437433/hpr2215_STI_NCSP_v6.pdf. United Kingdom National Guideline on the Management of Infection with Chlamydia trachomatis, 2015 Clinical Effectiveness Group (British Association for Sexual Health and HIV). United Kingdom National Guideline for the Management of gonorrhoea in adults, 2011 Clinical Effectiveness Group (British Associ- ation for Sexual Health and HIV). Sherrard Jackie, Ison Cathy, Moody Judith, Wainwright Emma, Wilson Janet, Sullivan Ann. United Kingdom national guideline for the management of Trichomonas vaginalis. Int J STD AIDS 2014; 25: 541e9. United Kingdom National Guideline for the Management of syphilis, 2008, Clinical Effectiveness Group (British Association for Sexual Health and HIV). United Kingdom National Guideline on the Management of Ano-genital warts, 2015, Clinical Effectiveness Group (British Association for Sexual Health and HIV). Management of genital herpes in pregnancy RCOG and BASHH 17/10/14. Published online: November 26, 2013. United Kingdom National Guideline on the Management of the viral hepatitides A, B & C, 2008, Clinical Effectiveness Group (British Association of Sexual Health and HIV). Practice points C Sexually Transmitted Infections are common in young women, often asymptomatic and can have serious consequences to mother and child in pregnancy. C Assess and reassess a woman’s risk of Sexually Transmitted In- fections regularly throughout pregnancy. C Management should be undertaken jointly with genitourinary physicians and paediatricians. REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 258 Ó 2016 Elsevier Ltd. All rights reserved.

8. Nutrition in pregnancy Alison Ho Angela C Flynn Dharmintra Pasupathy Abstract The pivotal role of nutrition in pregnancy is well established and has important implications on subsequent maternal and offspring health, including outcomes in later adult life. Optimal nutrition periconception, if maintained throughout pregnancy, promotes optimal foetal growth and development. Growth trajectories in utero and size at birth are related to the offspring’s risk of developing disease in later life, especially chronic non-communicable diseases such as hypertension, diabetes and coronary heart disease (the Barker hypothesis). This article aims to review nutritional requirements in pregnancy, describe their transport mechanisms and highlight the implications of inadequate or inappropriate intake. Nutritional requirements are broadly divided into issues surrounding quality (macronutrients and micronutrients) and quantity of intake with a final summary of current International Federation of Gynaecology and Obstetrics (FIGO) and Royal College of Obstetricians and Gynaecologists (RCOG) recommendations. Keywords gestational weight gain; healthy eating; macronutrients; micronutrients; nutrient requirements; nutrition; pregnancy Introduction The fetus relies on maternal nutrition for growth and development. Additionally, nutrition forms the basis of maternal well- being and equips the mother for delivery and recovery post- natally. Nutrition is recognized to be associated with gestational diabetes and pre-eclampsia and therefore improved nutritional intake has the potential to reduce these complications and their associated short and long term morbidities. During the antenatal period, healthcare professionals have regular contact with pregnant women therefore pregnancy is an opportunity to help establish healthy dietary habits that can potentially be adopted by her family, establishing a beneficial background to optimal health for future generations. The placenta links maternal and foetal circulation with syncytiotrophoblasts lining placental villi and consisting of two polarized membranes: microvillous membrane facing maternal circulation and basal plasma membrane facing foetal capillary epithelium. Thus, nutrients must pass through these two membranes before crossing the foetal capillary epithelium to enter the foetal circulation. The expression and activity of transporter mechanisms within the placental-foetal unit have been found to be associated with foetal growth restriction, macrosomia, diabetes, obesity and maternal nutrient availability. Healthy eating in pregnancy The National Institute for Health and Clinical Excellence (NICE) form the basis of UK healthcare policy and include healthy eating approaches. Calorie restriction is not advised and recommendations focus on achieving and maintaining a healthy weight during pregnancy by basing meals on starchy foods (wholegrain if possible), eating fibre rich foods and consuming at least five portions a day of fruit and vegetables. Food high in fat and sugar (including fried, some drinks and confectionery) should be avoided. Pregnant women are also advised to eat breakfast, and to watch portion sizes and how often they are eating. The RCOG has provided advice regarding healthy eating in pregnancy in alignment with NICE guidance. Low-fat dairy foods for a source of calcium are encouraged with a daily intake of protein in the form of lean meat, two portions of fish a week (one of which should be oily) or lentils, beans and tofu. The Gov- ernment’s Healthy Start voucher scheme has successfully improved dietary patterns in pregnancy with a reported relative increase in daily portions of fruit and vegetables. Nutrient requirements in pregnancy Energy and macronutrients Energy requirements in pregnancy for individuals vary and guidelines differ between countries, however, it is agreed that additional requirements are relatively small. The RCOG recommends a modest increase of 200 kcal/day in the third trimester e an approximate 10% increase from the 1940 kcal/day recommendation in a non-pregnant adult woman. Carbohydrate and fibre: carbohydrates form the main substrate for foetal growth, fuelling maternal and foetal organ function, biosynthesis and are additionally used in structural components of cells, co enzymes and DNA. Maternal and foetal brain functions use glucose from carbohydrate as their preferred source of energy with glucose providing at least 75% of foetal energy requirements. Glucose crosses the placenta by facilitated diffusion along a concentration gradient through members of the glucose transporter family (GLUT). Carbohydrate type and quantity can affect glucose homeostasis via release of insulin. The glycemic index (GI) refers to the area under the curve for blood glucose concentrations during a 2- h period after consuming a test food. A low GI suggests slower rates of digestion and absorption of a food’s carbohydrate, potentially relating to a lower insulin demand. It is therefore a modifiable macronutrient in the management of diabetes mellitus (gestational, type 1 and type 2), however, there is no evidence to support a low glycemic index diet for healthy pregnant women. Alison Ho MA MBBS is a Specialist Registrar in Obstetrics and Gynaecology at Kingston Hospital NHS Foundation Trust, London, UK. Conflicts of interest: none declared. Angela C Flynn BSc MSc is a Research Nutritionist at the Women’s Health Academic Centre, Division of Women’s Health, King’s College London, UK. Conflicts of interest: none declared. Dharmintra Pasupathy MSc PhD MRCOG is a Consultant/Senior Lecturer in Maternal and Fetal Medicine and Perinatal Epidemiology at the Women’s Health Academic Centre, Division of Women’s Health, King’s College London, UK. Conflicts of interest: none declared. REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 259 Ó 2016 Elsevier Ltd. All rights reserved.

9. Fibre affects the postprandial insulin response by influencing the accessibility of carbohydrates and nutrients to digestive enzymes thus delaying their absorption. Fibre supports maternal digestive health, providing bulk to stool and absorbing water to aid transit time. This is especially beneficial as progesterone levels in pregnancy can result in constipation by increasing relaxation of intestinal smooth muscle. Protein: protein forms the building blocks for both structural and functional components of cells. Requirements are highest during the second and third trimesters due to extra development and growth of both maternal and foetal tissue. It is an alternative energy source when carbohydrate intake is insufficient therefore adequate carbohydrate intake is required in order for cell synthesis to continue. Low socioeconomic status and women with limited dietary variety are at risk of suboptimal protein intake. Plasma concentrations of most amino acids are higher in foetal circulation. Over 15 different amino acid transporters mediate their transport against a concentration gradient. Systems include System A and System L. System A is sodium dependent for small neutral amino acids while System L is sodium inde- pendent for large neutral amino acids with branched or bulky side chains. Fats and essential fatty acids: fat aids transport of fat-soluble vitamins A, K, D and E and are required for structural (e.g. membrane lipids) and metabolic functions (e.g. precursor for steroid hormones). PUFAs (poly unsaturated fatty acids) are important for neurological development including foetal brain, nervous system and retina. Oily fish, nuts, seeds, vegetable oils, margarines and green leafy vegetables are encouraged to obtain a greater intake of PUFA. Essential fatty acids linoleic and alpha linolenic acid are pre- cursors for n-6, n-3 LCPUFA and prostaglandins; these are components of the inflammatory process with a role in diseases characterized by inflammation, reproductive health, cervical ripening and initiation of labour. Systematic reviews of RCTs have found little or no effect of n-3 LCPUFA supplementation in pregnancy on cognitive development, birth weight, gestational diabetes mellitus or pre-eclampsia. There is, however, a beneficial effect on increasing gestational length and reducing risk of preterm birth. Placental triglyceride lipases break down triglycerides into fatty acids. Fatty acids and ketone bodies (produced by maternal lipolysis) cross the placenta by diffusion. Cholesterol-carrying lipoproteins LDL, HDL and VLDL transport cholesterol into foetal circulation. Syncytiotrophoblasts express lipoprotein specific receptors e.g. LDL receptor, scavenger receptor class B type 1 and VLDL receptor. Binding cassette transporter A1 and GI in the foetal endothelium allow cholesterol to enter the foetal circulation. The fetus also synthesizes cholesterol endogenously. Micronutrients Iron and vitamin C: iron is a component of haemoglobin required for foetal development, placental growth and expansion of maternal red blood cell mass. Vulnerability to iron deficiency occurs, especially in late pregnancy as iron transfer to the fetus becomes marked in order to meet increased demands. Deficiency has been associated with a higher risk of preterm delivery, low birth weight, infant iron deficiency and long-term cognition and brain function. Replete stores are required in preparation for childbirth as significant blood loss may occur intrapartum. Iron transfer to the fetus is facilitated through placental transferrin receptors for endocytosis of transferrin- bound iron. Vitamin C aids iron absorption and competes for placental receptors with glucose, however maternal hyperglycaemia does not result in foetal hypovitaminosis C. A recent Cochrane review suggested that vitamin C might have a role in preventing placental abruption (RR 0.64, 95% CI 0.44e0.92) and prelabour rupture of membranes (RR 0.98, 95% CI 0.70e1.36). However, women supplemented with vitamin C alone or in combination with other supplements were more likely to self-report abdominal pain. Gestational age at birth was increased amongst these women. Supplementation with vitamin C alone reduced the risk of preterm PROM and term PROM but the risk of term PROM was increased when supplementation included vitamin C with vitamin E. The risk of stillbirth, neonatal death, IUGR and pre-eclampsia were not affected by vitamin C supplementation. Folate and vitamin B12: the prevention of neural tube defects with periconceptional folic acid is well established. Folic acid supplementation has no clear effect on cleft palate/lip or congenital cardiovascular defects. Five percent of the general population has marginal to severe folate deficiency and therefore all women are advised to take 400 mcg/day folic acid prior to conception until the 13th week of pregnancy with higher doses in certain circumstances (Table 1). Folate binding receptors maintain a high foetalematernal concentration gradient for DNA synthesis while vitamin B12 is transported via placental receptors. Both micronutrients are associated with a reduction in megaloblastic anaemia, placental vascular disorders, preterm birth, low birth weight and SGA via regulation of circulating homocysteine levels. Homocysteine levels are influenced by the activity of meth- ylene tetrahydrofolate reductase (MTHFR). The C6777T variant has impaired MTHFR function and its presence is associated with an increased risk for pre-eclampsia and recurrent pregnancy loss, potentially via elevated homocysteine levels. Low dietary intake of folic acid can exacerbate this but evidence is lacking with regard to whether pregnant women carrying the C6777T variant should take a higher folic acid supplement. Vitamin D and calcium: vitamin D is required for immune and nervous system function and mediates the accumulation of foetal calcium from maternal stores in skeletal growth. Vitamin D deficiency can result in rickets, craniotabes and osteopenia. Calcium supplementation reduces the development of hypertensive disorders of pregnancy and an increasing body of evidence demonstrates a relationship between vitamin D deficiency REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 260 Ó 2016 Elsevier Ltd. All rights reserved.

10. Dietary recommendations in pre-pregnancy and pregnancy (per day) Pre-pregnancy Pregnancy Food sources Macronutrients Energy 1940 kcal þ200 kcal in third trimester only Carbohydrates in starchy vegetables, grains, sugars. Fat in nuts, seeds, vegetable oils, poultry, eggs, fish, meat Fibre No quantitative recommendation Beans, wholegrain, wholemeal, pulses, nuts, oats, fruit and vegetables Protein 45 g þ6 g Meat, poultry, fish, eggs, dairy products, legumes, rains, nuts, seeds Micronutrients Thiamin 0.8 mg þ0.1 mga Vegetables (peas), fruit, eggs, wholegrain breads, some fortified breakfast cereals, livere Riboflavin 1.1 mg þ0.3 mg Milk, eggs, fortified breakfast cereals, rice Vitamin C 40 mg þ10 mg Fruit, vegetables Folate 200 mg þ100 mgb Broccoli, Brussels sprouts, livere , spinach, asparagus, peas, chickpeas, fortified breakfast cereals Vitamin D e þ10 mgc Oily fish, eggs, fortified fat spreads, fortified breakfast cereals, some powdered milks Vitamin A 600 mg þ100 mg Cheese, eggs, oily fish, fortified low-fat spreads, milk, yoghurt Niacin 13 mg d Meat, fish, wheat flour, eggs, milk Vitamin B6 1.2 mg d Pork, poultry, fish, bread, whole cereals, eggs, vegetables, soya beans, peanuts, milk, potatoes, some fortified breakfast cereals Vitamin B12 1.5 g d Meat, salmon, cod, milk, cheese, eggs, some fortified breakfast cereals Calcium 700 mg d Dairy products, green leafy vegetables, soya beans, tofu, nuts, bread with fortified flour, sardines and pilchards Phosphorus 550 mg d Red meat, diary foods, fish, poultry, bread, brown rice, oats Magnesium 270 mg d Green leafy vegetables, nuts, brown rice, bread (especially wholegrain), fish meat, dairy foods Sodium 1600 mg d Sodium chloride naturally low levels in all foods but added to processed foods e.g. ready meals, meat products (bacon), cheese, some bread, breakfast cereals, savoury snacks, tinned vegetables Chloride 2500 mg d Potassium 3500 mg d Fruit (bananas), some vegetables (broccoli, parsnips, brussel sprouts), pulses, nuts, seeds, fish, shellfish, beef, chicken turkey Iron 14.8 mg d Livere , meat, beans, nuts, dried fruit, wholegrains, fortified breakfast cereals, soybean flour, dark-green leafy vegetables (continued on next page) REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 261 Ó 2016 Elsevier Ltd. All rights reserved.

11. and low birth weight, preterm delivery, gestational diabetes mellitus and pre-eclampsia. Individuals particularly at risk for vitamin D deficiency include those of South Asian, African, Caribbean or Middle Eastern origin, a body mass index >30 kg/ m2 and low sun exposure. Iodine: iodine is required for foetal thyroid function and neurological development. Iodine deficiency has been linked to mental retardation and cognitive deficit. Periconceptional and antenatal supplementation in regions of severe iodine deficiency have been found to reduce the risk of cretinism and improve motor function. Reports of gestational iodine deficiency and potential benefits of iodine supplementation are emerging. Vitamin E: more evidence regarding vitamin E supplementation in pregnancy is required, as a recent Cochrane review suggested an advantageous role in reducing the risk of placental abruption (RR 0.64, 95% CI 0.44e0.93). However, supplementation with vitamin E was associated with an increased risk of self-reported abdominal pain and term prelabour rupture of membranes. There was no difference in vitamin E supplementation on the risk of stillbirth, pre- eclampsia, preterm birth and IUGR. Gestational weight gain and obesity in pregnancy To achieve appropriate gestational weight gain, the provision of energy is balanced against physical activity, pre-pregnancy weight, age, nutritional status, percent of body fat to fat free mass, basal metabolic rate with energy expenditure to support growth and development of the placental-foetal unit. The relationship between gestational weight gain and pregnancy outcomes is difficult to establish, as it is a reflection of multiple components: fetus, placenta, uterus, amniotic fluid, maternal adipose tissue, blood volume expansion and mammary glands. NICE have not published recommendations on weight gain during pregnancy due to lacking evidence, however, the recommendation of the Institute of Medicine (2009) are detailed in Table 2. A high pre-pregnancy BMI carries adverse maternal and foetal outcomes e gestational diabetes mellitus, pre-eclampsia, Table 1 (continued) Pre-pregnancy Pregnancy Food sources Zinc 7.0 mg d Meat, shellfish, dairy foods, bread, cereal products Copper 1.2 mg d Nuts, shellfish, offal Selenium 60 mg d Brazil nuts, fish, meat, eggs Iodine 140 mg d Sea fish, shellfish, cereals, grains Other points to note Oily fish (source of omega 3 fatty acids): Two portions of fish a week, one of which should be oily. Caffeine: <200 mg/day (¼roughly two mugs of instant coffee). a In third trimester only. b 400 mg folic acid/day supplement pre conception until 13 weeks. Higher dose of 5 mg folic acid/day supplement pre conception until 13 weeks if patient or partner has a neural tube defect or family history of neural tube defects, previous pregnancy affected by neural tube defect, BMI >30 kg/m2 , coeliac disease, diabetes or on anti- epileptic medication, sickle-cell anaemia or thalassaemia. c 10 mg supplement is required as this level is not usually achievable through diet. Especially important for those most at risk of deficiency: women of South Asian, African, Caribbean or Middle Eastern family origin, limited exposure to sunlight, diet low in vitamin D (e.g. those women who consume no oily fish, eggs, meat, vitamin D-fortified margarine or breakfast cereal), prepregnancy body mass index >30 kg/m2 . d No increment. e Liver is high in vitamin A and high consumption is not recommended in the periconceptional period due to the teratogenic risk. Obtained from Nutrition in Pregnancy Scientific Impact Paper No. 18 2010. RCOG 2010 and www.nhs.uk Table 1 IOM recommendations on total weight gain during pregnancy for singleton fetuses Pre-pregnancy body mass index (BMI) (kg/m2 ) Total weight gain during pregnancy (lbs) Total weight gain during pregnancy (kgs) Underweight <18.5 28e40 13e18 Normal weight 18.5e24.9 25e35 11e16 Overweight 25.0e29.9 15e25 7e11 Obese 30 11e20 5e9 Obtained from Weight Gain During Pregnancy: Reexamining the Guidelines IOM report May 2009 Table 2 REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 262 Ó 2016 Elsevier Ltd. All rights reserved.

12. caesarean section, assisted delivery, postpartum haemorrhage, infection and thrombosis, large for gestational age (LGA) growth, birth defects and stillbirth. Periconception and antenatally, these women should be warned of these increased risks and encouraged to make lifestyle changes to support weight management. Randomized controlled trials of physical activity and dietary intervention in obese women have failed to demonstrate an effect on the risk of gestational diabetes and LGA. Further research is required to determine the optimal gestational weight gain in different BMI categories. Special considerations Smoking, alcohol and caffeine consumption and recreational drug use can have a detrimental effect on foetal nutrition, growth and development. Physical activity is beneficial by managing weight gain, preparing for labour and aiding glucose homeostasis especially in diabetic women. Pregnant women are at risk of food borne illness e.g. listeri- osis in unpasteurized milk, cheese or pate, salmonella in partially cooked eggs, poultry and shellfish and toxoplasmosis in undercooked meat or salad vegetables contaminated with soil or contamination with cat faeces. Methylmercury in fish is teratogenic, affecting development of the foetal nervous system, and therefore should be restricted to two portions a week. Consuming high levels of vitamin A is also teratogenic and therefore multi-vitamins containing vitamin A, liver, pate, fish liver oils and other food fortified with vitamin A should be avoided. FIGO recommendations The recent FIGO recommendations in adolescent, pre conception and maternal nutrition have emphasized that healthcare promotion is the cornerstone of optimizing nutritional status (Box 1). Conclusion Nutrition in pregnancy requires a careful balance of both quality and quantity of intake in order to optimize foetal growth and development in addition to reducing maternal morbidity. MTHFR genotypes, vitamin C, vitamin E and iodine supplementation are emerging areas of research. The RCOG and FIGO recommendations have centered around early intervention through healthcare promotion of a varied, healthy diet, beneficial lifestyle behaviours and the use of supplementation or fortified foods as necessary. Such changes are also valuable if carried out in the long term by both the mother and her family. A FURTHER READING Barker DJ. Maternal nutrition, fetal nutrition and disease in later life. Nutrition 1997 Sep; 13: 807e13. Bothwell TH. Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr 2000 Jul; 72(suppl 1): 257se64. De-Regil LM, Pena-Rosas JP, Fernandez-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2015 Dec 14. Issue 12. Art. No.:CD007950. Hanson MA, Bardsley A, De-Regil LM, et al. The International Federation of Gynecology and Obstetrics (FIGO) recommendations on adolescent, preconception, and maternal nutrition: “Think Nutrition First”. Int J Gynaecol Obstet 2015 Oct; 131(suppl 4): S213e53. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev 2014 Jun 24. Issue 6. Art. No.:CD001059. National Institute for Health and Care Excellence. Weight management before, during and after pregnancy. NICE guidelines published July 2010. PH27. https://www.nice.org.uk/guidance/ph27/resources. Royal College of Obstetricians Gynaecologists. Nutrition in pregnancy (Scientific Impact Paper No. 18). RCOG published 2010. https://www.rcog.org.uk/en/guidelines-research-services/ guidelines/sip18/. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev 2015. Issue 9. Art. No.:CD004072. Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev 2015. Issue 9. Art. No.:CD004069. FIGO recommendations in pregnancy Obtained from Hanson MA, Bardsley A, De-Regil LM et al. The Inter- national Federation of Gynaecology and Obstetrics (FIGO) recommendations on adolescent, preconception, and maternal nutrition: “Think Nutrition First”. Int J Gynaecol Obstet 131 S4(2015) S213 eS253. 1. Promotion of a varied, healthy diet with supplementation or fortification of foods when necessary 2. Encouraging the adoption of healthy dietary habits pre-pregnancy 3. Early access to prenatal care to provide the following: a. nutrition counselling b. recognition and appropriate intervention of micronutrient deficiencies c. treatment of co-existing conditions e.g. malaria, TB, HIV, gastrointestinal infections and non-communicable disease 4. Importance of pre-pregnancy BMI a. Both low and high BMIs may lack either nutritional quality or quantity balance, resulting in poorer pregnancy outcomes 5. Avoidance of detrimental behaviours including smoking, alcohol intake and recreational drug use before, during and after pregnancy as well as food borne illness and teratogens 6. Exercise and energy requirement recommendations a. dietary energy intake should only involve a moderate increase of 340e450 kcal per day in the second and third trimester b. moderate exercise of 30 minutes per day and avoidance of hard physical labour during late pregnancy 7. Monitoring of appropriate gestational weight gain Box 1 REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 263 Ó 2016 Elsevier Ltd. All rights reserved.

13. Practice points C Advice regarding nutrition in pregnancy centers around a healthy, varied diet pre-pregnancy, antenatally and post-natally C Important components include macronutrients (carbohydrate, fibre, protein, fats) and micronutrients (iron, folate, vitamin B12, vitamin D, calcium, iodine) C Energy requirements in pregnancy require a modest increase of 200 kcal/day in the third trimester C A high fibre, low glycemic index diet aids glucose homeostasis in diabetic women C PUFAs may beneficially increase gestational length and reduce risk of preterm birth through their role in inflammation C Increased vulnerability to iron deficiency occurs in the 3rd trimester and replete stores are required in preparation for intrapartum blood loss C The role of vitamin C and E supplementation in reducing placental abruption and prelabour rupture of membranes requires further research C Calcium supplementation reduces the development of hypertensive disorders of pregnancy C Vitamin D deficiency has been found to be associated with low birth weight, preterm delivery, gestational diabetes mellitus and pre-eclampsia C Potential benefits of iodine supplementation are emerging C Obesity and excessive gestational weight gain are associated with adverse maternal and foetal outcomes, however, optimal gestational weight gain in different BMI categories are yet to be determined by NICE C Food can carry teratogens (mercury, lead) and pathogens (liste- riosis, salmonella, toxoplasmosis) C Smoking, alcohol intake and recreational drug use are detrimental behaviours that should be avoided REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 264 Ó 2016 Elsevier Ltd. All rights reserved.

14. Routine antenatal management later in pregnancy Louise-Emma Shaw Lucy H Kean Abstract Routine antenatal care in later pregnancy is geared towards the detection of problems requiring specialist input and the reassurance that pregnancy is progressing well when no problems are identified. This review follows on from ‘routine antenatal management at the booking clinic’, and assesses the specific tasks and investigations that are routine for all women in later pregnancy. Keywords problem-free pregnancy; routine antenatal care; screening in obstetrics Introduction The antenatal care of pregnant women continues routinely after the initial booking visit. This review focuses on the antenatal care that is offered later in pregnancy and discusses areas of antenatal care that have been shown to be beneficial. If the pregnancy is determined to be problem-free at the booking clinic, routine later care must be aimed at ensuring that the pregnancy continues in the same uncomplicated way or, if it is not, at identifying complications as they arise and initiating further investigations and treatment as necessary. Why provide antenatal care? In its infancy, antenatal care was thought to reduce maternal and perinatal mortality. This belief was reinforced by the finding that the more visits a woman made to the antenatal clinic, the better the pregnancy outcome. This of course did not allow for the fact that women whose pregnancies ended early could only make correspondingly fewer visits. Additionally, critical reviews of antenatal care have failed to establish a link between care and improved pregnancy outcome, particularly in women with uncomplicated pregnancies. However, uncomplicated pregnancies are only so labelled until complications arise, making interpre- tation of historical studies difficult. One third of maternal deaths between 2009 and 2013 had issues with access or uptake of antenatal care. What pattern of care is effective? The traditional pattern of antenatal care provided for is up to 15 visits during pregnancy. It was originally formulated in 1929 and arose from a collation of the view of doctors offering antenatal care at the time. It was not based on any scientific evidence, and remained the most commonly used pattern of care in the UK until relatively recently. Anxiety about reduced numbers of visits stemmed mainly from retrospective studies showing that important diagnoses may be missed. However, the fact that across Europe, equal if not better perinatal mortality rates are achieved with fewer visits has made this idea more acceptable and led to its evaluation by randomised controlled trials (RCTs). There are now seven RCTs and a Cochrane review addressing reduced or tailored patterns of visits for women with problem-free pregnancies. However, women are significantly more likely to feel that their care has been less good, and to report more problems in caring for their infants if they receive a reduced schedule of care. As a result they have a longer postnatal stay which negates any cost savings from the reduced schedule of care. Evaluation of the type of caregivers to whom women are allo- cated has also been undertaken. This has generally been a com- parisonoftraditional‘sharedcare’involvingthehospitalconsultant team, general practitioner and community midwives, with a programme encompassing midwifery care with or without general practitioner involvement. Three well-conducted RCTs have compared types of care for low-risk women. These studies have shown that women receive marginally fewer visits in community- led schedules, are generally less likely to be admitted, and have greater levels of satisfaction with their care. In studies in which care was continued into labour, less analgesia was needed, fewer epi- siotomies were performed and the first stage was usually shorter than in women for whom shared care was the norm. Women are more satisfied with most aspects of their care if they are cared for in a community setting, but these studies also show that reducing the total numbers of visits may cause problems in terms of women’s perception of their ability to cope both ante- and post-natally. A Cochrane review also reported that there is no significant improvement in pregnancy outcome in women with problem- free pregnancies who routinely see an obstetrician. Therefore, community midwifery and GP-led care should be routinely offered to women with uncomplicated pregnancies. The frequency of follow-up visits for women with problem- free pregnancies can safely be conducted at approximately monthly intervals without compromising the safety of the mother or fetus. However, at each visit it is important that clinically necessary tasks are undertaken. These vary slightly with gestation. The National Institute for Clinical Excellence (NICE) guideline “Antenatal care: routine care for the health pregnant woman” outlines the suggested schedule of visits and the tasks to be undertaken at each. These include visits at 16 weeks, the anomaly scan at 18e20 weeks (discussed in “Routine antenatal management at the booking clinic”), 28 weeks, 34 weeks, 36 weeks, 38 weeks, and 41 weeks. Additional visits are suggested at 25 weeks, 31 weeks, and 40 weeks for nulliparous women. It must be stressed that this schedule of care is solely for women for whom risk factors have not been identified. Women with risk factors for a poorer pregnancy outcome must have care tailored to their particular circumstances. Louise-Emma Shaw MRCOG is a Specialist Registrar at Nottingham University Hospitals NHS Trust, Nottingham, UK. Conflicts of interest: none declared. Lucy H Kean MA DM FRCOG is a Consultant Obstetrician (Subspecialist in Fetal-Maternal Medicine) at Nottingham University Hospitals NHS Trust, Nottingham, UK. Conflicts of interest: none declared. REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 265 Ó 2016 Elsevier Ltd. All rights reserved.

15. Screening for clinical problems In later pregnancy, the routine antenatal care of women with problem-free pregnancies is geared towards detection of clinical problems. This is so that investigations and, if necessary, treatment can be offered. This usually involves referring the woman to the hospital so that an obstetrician can be involved. The main aims of routine antenatal care in later pregnancy are to detect the common and treatable disorders of pregnancy. National policy regarding screening for gestational diabetes mellitus (GDM) has changed significantly recently in the light of new evidence. Monitoring fetal growth The two clinical methods used to assess fetal growth are symphysis fundal height (SFH) measurement and abdominal palpation. Abdominal palpation has limited accuracy for the prediction of a small-for-gestational age (SGA) neonate and thus should not be routinely performed in this context. Serial measurement of symphysis fundal height (SFH) is recommended at each antenatal appointment from 24 weeks of pregnancy as this improves prediction of a SGA neonate. SFH should be plotted on a customised rather than a population-based chart as this may improve the prediction of a SGA neonate. Women with a single SFH which plots below the 10th centile or serial measurements which demonstrate slow or static growth by crossing centiles should be referred for ultrasound measurement of fetal size. SFH measurements (in centimetres) give a more objective assessment of uterine size, and serial measurements enable us to observe the fetal growth rate. Controlled trials compared SFH measurements against abdominal palpation alone and showed no differences in pregnancy outcomes, including perinatal mortality, umbilical artery pH less than 7.15, neonatal care admissions, induction of labour for intrauterine growth restriction (IUGR), Caesarean section for IUGR and birth weight below the 10th centile. The sensitivity of SFH measurement may be as low as 27% although its specificity around 85e90%. However, it is a cheap tool in antenatal care, requiring minimal equipment, training and time. Despite its shortcomings, NICE guidelines recommend that SFH should be routinely measured and plotted to assess fetal growth at each antenatal visit. Many practitioners have been taught that SFH in centimetres should approximate to gestation. This is not quite the case. SFH is usually a little less than this, as can be seen in Figure 1 Calvert et al. (1982). There is some evidence that customised growth charts may improve detection of IUGR (and reduce clinic referrals for suspected small for gestational age), but this has yet to be established in prospective studies in large populations. Women in whom SFH measurement is inaccurate (e.g. BMI 35, large fi- broids, hydramnios) should be referred for serial assessment of fetal size using ultrasound. No trials were identified that compared customised with non- customised SFH charts and thus evidence for their effectiveness on outcomes such as perinatal morbidity/mortality is lacking. However, observational studies suggest that customised SFH charts may improve the detection of a SGA neonate and where these charts have been widely used a drop in the perinatal mortality rate has been observed. If three or more minor risk factors for SGA were identified at booking, uterine artery Dopplers should be undertaken between 20 and 24 weeks. If normal, assessment of fetal size and umbilical artery Dopplers should be done in the third trimester. If uterine artery Dopplers are abnormal then serial assessment of fetal size and umbilical artery Dopplers should be performed from 26 to 28 weeks. In the presence of one major risk factor for SGA, serial assessment of fetal growth and umbilical artery Dopplers should be instigated from 26 to 28 weeks. Detection of hypertensive disorders of pregnancy The hypertensive disorders of pregnancy are categorized as gestational hypertension (GH), in which the first onset of hypertension is during pregnancy and it resolves after delivery with no proteinuria, and pre-eclampsia (PET), which is a more serious condition associated with increased maternal and neonatal morbidity and mortality. PET is a multi-system disorder defined as the first onset of hypertension after 20 weeks’ gestation associated with proteinuria (in the absence of urinary tract infection), which resolves after delivery. The incidence is 2e10% depending on the population and the diagnostic criteria used. Eclampsia is rare, with an estimated incidence in the UK of 21/100,000 pregnancies, based on recent UKOSS data. Of the 19 deaths, in the triennium 2006e2008, 14 died from intracranial haemorrhage and five from anoxia as a result of cardiac arrest following eclamptic seizures. Worryingly, 14 were considered to have received major substandard care due to inadequate anti- hypertensive therapy and failure of referral from the community for specialist care. There were six further maternal deaths from pre-eclampsia and eclampsia in 2011e2013. Blood pressure varies throughout pregnancy. Hypertension in pregnancy is definedastworeadingsof140/90 mmHg taken at least 4 hoursapart, using Korotkoff V for the diastolic sound.An absolute value appears to correlate with clinical outcome much more strongly than an incremental rise in gestational blood pressure. To differentiate between GH and PET, it is important to detect the presence of proteinuria. The diagnosis of PET requires the presence of significant proteinuria along with high blood pressure. A simple screening test for proteinuria is urinalysis using reagent strips (‘dipstick’). As false-positive results (6%) can occur, it is important that a result of 1þ or more should be confirmed by further tests. While urine protein:creatinine ratio appeared in a recent systematic review to be a good method for ‘ruling out’ significant proteinuria, using a threshold of 30 mg/mmol, a result at or above this threshold should normally lead to quantification of proteinuria by 24 hour collection and usually inpatient assessment. Quantitative assessment of proteinuria using a point of care test is recommended in settings where urine testing is widely performed such as antenatal clinic and day assessment units, as this can limit the number of quantitative tests sent to the laboratory. A finding of 0.3 g/24 hours of protein or more is considered significant. Blood pressure should be measured and urinalysis for proteinuria should be undertaken routinely at each antenatal visit. It must be remembered, however, that PET can present with proteinuria without hypertension initially or hypertension without proteinuria, so increased vigilance is required in any woman with 1þ proteinuria or a blood pressure of 140/90 mmHg. If significant proteinuria and hypertension is present, mothers are best managed as an inpatient (Tables 1 and 2). The presence of symptoms suggestive of PET such as headache, epigastric pain, vomiting or visual disturbance should prompt further evaluation REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 266 Ó 2016 Elsevier Ltd. All rights reserved.

16. and consideration of admission. A blood pressure of 150/100 mmHg or more will need treatment with antihypertensives. Oral labetalol should be the first line of management. With BP of 150/ 100 mmHg or more, admission to hospital and blood tests e full blood count, renal function, electrolytes, transaminases, and bilirubin should be done three times a week, BP should be monitored more than four times a day (Table 3). A recent randomised controlled trial comparing induction of labour versus expectant monitoring for women with gestational hypertension (defined as diastolic BP of 95 mmHg or more on two occasions 6 hours apart) and mild PET (defined as diastolic BP of 90 mmHg or more on two occasions plus proteinuria of 300 mg/24 hours or a protein creatinine ratio of 30 mg/mmol) showed that induction of labour at 37 or more weeks was associated with a lower incidence of maternal adverse events with no increase in the rate of Caesarean section in the induced group. Therefore, for women with new onset hypertension after 37 weeks, induction should be considered unless the disadvantages of induction outweigh the advantages. Anaemia The normal maternal haemoglobin level is above 11 g/dL at around 28 weeks’ gestation. Therefore, screening for anaemia should be routinely performed at 28 weeks’. NICE guidelines do not recommend routine screening for anaemia after this gestation. Any deviation from the norm should prompt appropriate investigations and treatment. Figure 2 shows a suggested algo- rithm for haemoglobin testing and management. Red cell antibody screening and prophylactic anti-D Repeat blood test screening for atypical red cell alloantibodies should be conducted at around 28 weeks’ gestation. The 2008 NICE guidelines do not recommend any further routine screening. However, in women who have red cell antibodies detected, further screening (and possibly fetal surveillance and/ or treatment) may be recommended by the reporting blood laboratory. Despite screening and administration of anti-D after sensi- tising events, 1e1.5% of Rh-D-negative women still develop anti-D antibodies during pregnancy, usually because of small, asymptomatic (or unrecognised) feto-maternal haemorrhages occurring in the last trimester. For these women, postnatal prophylaxis is too late. Studies in Canada, the UK and France have shown that routine antenatal prophylaxis can reduce sensitisation to 0.2% or less, provided that sufficient anti-D immunoglobulin (Ig) is given. Administration of 500 IU anti-D Ig at 28 and 34 weeks’ gestation has been shown to reduce the incidence of immunisation at 2e12 months after birth (OR 0.22, 95% CI 0.05e0.88). Given that there is now a sufficient supply of anti-D Ig available, NICE have recommended that routine antenatal prophylaxis should be offered to all Rh-D- negative women. However, if the biological father is known not to be Rhesus positive, then prophylaxis will not be needed. Other situations where NICE guidelines consider that antenatal anti-D prophylaxis may not be necessary include cases where a woman has opted to be sterilised after the birth of the baby or when a woman is otherwise certain that she will not have another child after the current pregnancy. It is current practice to administer two doses of anti-D Ig, one at 28 and one at 34 weeks’ gestation (usually 500 IU, although the dose given de- pends on the preparation used), with measurement of the anti-D titre just before administration, or to give a single dose of 1500 IU at 28 weeks’ gestation. Screening for gestational diabetes mellitus (GDM) Until the revision of the NICE Guideline on Antenatal Care, there had been no national guideline on screening for GDM, and many different hospitals employed different screening practices, Management of pregnancy with pre-eclampsia Degree of hypertension Mild hypertension (140/90 to 149/99 mmHg) Moderate hypertension (150/100 to 159/109 mmHg) Severe hypertension (160/110 mmHg or higher) Admit to hospital Yes Yes Yes Treat No With oral labetalol as first-line treatment to keep: C diastolic blood pressure between 80e100 mmHg C systolic blood pressure less than 150 mmHg With oral labetalol as first-line treatment to keep: C diastolic blood pressure between 80e100 mmHg C systolic blood pressure less than 150 mmHg Measure blood pressure At least four times a day At least four times a day More than four times a day, depending on clinical circumstances Test for proteinuria Do not repeat quantification of proteinuria Do not repeat quantification of proteinuria Do not repeat quantification of proteinuria Blood tests Monitor using the following tests twice a week: kidney function, electrolytes, full blood count, transaminases, bilirubin Monitor using the following tests three times a week: kidney function, electrolytes, full blood count, transaminases, bilirubin Monitor using the following tests three times a week: kidney function, electrolytes, full blood count, transaminases, bilirubin NICE clinical guideline 107 e Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. Table 1 REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 267 Ó 2016 Elsevier Ltd. All rights reserved.

17. including no screening. The recent Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) trial showed that women treated for gestational diabetes had a significantly lower rate of serious perinatal complications compared with women with routine care (1% vs. 4%; p ¼ 0.01). These women had a higher rate of induction of labour than the women in the routine care group (39% vs. 29%) but no significant difference in Caesarean section rates (31% vs. 32%). The 2015 NICE guideline recommends screening for GDM on the basis of the following risk factors: body mass index above 30 kg/m2 previous macrosomic baby weighing 4.5 kg or above previous gestational diabetes family history of diabetes (first-degree relative with diabetes) family origin with a high prevalence of diabetes: South Asian (specifically women whose country of family origin is India, Pakistan or Bangladesh) black Caribbean Middle Eastern (specifically women whose country of family origin is Saudi Arabia, United Arab Emirates, Protein readings Dipstick protein reading Protein excretion g/24 hours Protein excretion mg/dL Negative 0.1 10 Trace 0.1e0.2 15 1þ 0.2e0.5 30 2þ 0.5e1.5 100 3þ 2.0e5.0 300 4þ 5.0 1000 Table 2 Community monitoring of hypertension: thresholds for further action Description Definition Action by midwife/general practitioner PRECOG grade New hypertension without proteinuria after 20 weeks Diastolic BP 90 to 100 mmHg Refer for hospital step-up assessment within 48 hour C Diastolic BP 90 to 100 mmHg with significant symptomsa Refer for same-day hospital step-up assessment C Systolic BP 160 mmHg Refer for same-day hospital step-up assessment C Diastolic BP 100 mmHg Refer for same-day hospital step-up assessment C New hypertension and proteinuria after 20 weeks Diastolic BP 90 mmHg and new proteinuria 1þ on dipstick Refer for same-day hospital step-up assessment A Diastolic BP 110 mmHg and new proteinuria 1þ on dipstick Arrange immediate admission A Systolic BP 170 mmHg and new proteinuria 1þ on dipstick Arrange immediate admission A Diastolic BP 90 mmHg and new proteinuria 1þ on dipstick, and significant symptomsa Arrange immediate admission A New proteinuria without hypertension after 20 weeks 1þ on dipstick Repeat pre-eclampsia assessment in community within 1 week C 2þ or more on dipstick Refer for hospital step-up assessment within 48 hour C 1þ on dipstick with significant symptomsa Refer for same-day hospital step-up assessment C Maternal symptoms or fetal signs and symptoms without new hypertension or proteinuria Headache and/or visual disturbances with diastolic BP pressure 90 mmHg and a trace of or no protein Follow local protocols for investigation; consider reducing interval before next PRECOG assessment C Epigastric pain with diastolic BP 90 mmHg and a trace of or no protein Refer for same-day hospital step-up assessment C Reduced movements or small for gestational age infant Follow local protocols for investigation of fetal compromise; consider reducing C with diastolic BP 90 mmHg and a trace of or no protein interval before next full pre-eclampsia assessment PRECOG, Pre-eclampsia Community Guideline. a Epigastric pain, vomiting, headache, visual disturbances, reduced fetal movements, small for gestational age. Table 3 REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 268 Ó 2016 Elsevier Ltd. All rights reserved.

18. Iraq, Jordan, Syria, Oman, Qatar, Kuwait, Lebanon or Egypt). In addition women who have glycosuria of 2þ on one occa- sion or 1þ on 2 occasions on dipstick testing should also be further investigated for gestational diabetes. Women with a BMI more than 40 or women or with a previous history of gestational diabetes should be offered a glucose tolerance test (GTT) early in the pregnancy and certainly by 16 e18 weeks gestation. If the results are normal a repeat GTT should be performed at 24e28 weeks. In order to make an informed decision about screening, NICE recommends that women should be informed, before deciding whether to have screening, that: in most women, gestational diabetes will respond to changes in diet and exercise some women (between 10% and 20%) will need oral hypoglycaemic agents or insulin therapy if diet and exercise are not effective in controlling GDM if GDM is not detected and controlled there is a small risk of birth complications such as shoulder dystocia a diagnosis of GDM may lead to increased monitoring and interventions during both pregnancy and labour. This guideline recommends the use of the 2 hour 75 g oral glucose tolerance test (OGTT) to test for gestational diabetes and diagnosis made using the criteria defined by the World Health Organization (fasting plasma venous glucose concentration greater than or equal to 5.6 mmol/L or 2 hour plasma venous glucose concentration greater than or equal to 7.8 mmol/L). While the ACHOIS trial suggested a benefit for screening and treatment, the precise level of hyperglycaemia that carries an increased pregnancy risk remains to be defined. However, the results of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study suggested a continuum of risk with increasing levels of maternal hyperglycaemia, including those below the usual threshold for a diagnosis of diabetes mellitus. Vaccination in pregnancy Seasonal influenza vaccine should be offered to every pregnant woman. Whooping cough vaccine should be offered between 28 and 38 weeks gestation. Maternal death from influenza has decreased with no deaths in 2012e2013 but this is felt to be a reflection of low influenza activity, and vaccination must remain a priority. Pregnant women are considered a high-risk group for severe influenza infection caused by the H1N1 virus. In the current influenza season, pregnant women are still likely to be exposed to this virus, with a risk of severe or complicated disease. Pregnant women are now well recognised as being at significantly increased risk of complications from H1N1 influenza infection; they are at greater risk of hospitalisation and during the influenza season a number of pregnant women have been in intensive care or received Extra Corporeal Membrane Oxygenation (ECMO). The mortality rate is several times higher than that for non-pregnant women in the same age group. The greatest risk is of severe chest infection, due to the flu itself, or to secondary bacterial infection-commonest in the second and third trimesters of pregnancy. Increased severity from influenza H1N1 infection in pregnancy is associated with pre-existing asthma, maternal smoking and obesity. Pregnant women admitted to hospital with H1N1 infection are (three times) more likely to deliver preterm and their babies are (five times) more likely to be stillborn or die in the first week of life. Pregnant women should avoid the risk of severe feverish illness at any stage of pregnancy. It is important to remember that flu can cause other types of illness at any stage, including diarrhoea and/or vomiting, muscle and joint inflammation and rarely, meningitis. Pertussis (whooping cough) is an infectious respiratory disease characterised by intense, heavy coughing. Adults who are infected are treated with antibiotics and advised to stay away from others to prevent contagion. Infants, because their immune systems are still developing, are at greater risk of serious complications such as pneumonia which could lead to death if they get whooping cough. For this reason, babies are routinely immunised from the age of 2 months. In adulthood, immune status, even for vaccinated individuals, wanes. Recently, there has been an increase in the numbers of cases of whooping cough. Deaths have occurred in babies that are too young to be immunised. Theoretically, boosting maternal antibodies during the latter stages of pregnancy should enhance neonatal protection. Hence the Department of Health recommends immunising all women from the 28th week of pregnancy to enable better protection for all newborns at birth. All pregnant women can access vaccination via their general practitioners. Checking for fetal presentation A check for presentation need not be performed until 36 weeks’ gestation, as a breech presentation is relatively common prior to this and the majority of breech-presenting fetuses will undergo spontaneous version to cephalic by 36 weeks. If there are doubts at this gestation, or if malpresentation is suspected, the woman can be referred to hospital for assessment, and if breech or some other malpresentation is confirmed, management op- tions can be discussed including, for example, external cephalic version. BMI should be reassessed in the third trimester in overweight women All women with a BMI over 30 should be advised on weight management during pregnancy. Obesity in pregnancy is associated with increased risks of GH, GDM, thromboembolism and maternal death. Weight management should be through healthy eating and moderate exercise. Women with a booking BMI 40 should have a documented assessment in the third trimester of pregnancy by an appropriately qualified professional to determine manual handling requirements for childbirth and consider tissue viability issues. Pregnant women with a booking BMI 40 should have an antenatal consultation with an obstetric anaesthetist, so that potential difficulties with venous access, regional or general anaesthesia can be identified. An anaesthetic management plan for labour and delivery should be discussed and documented in the medical records. REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 269 Ó 2016 Elsevier Ltd. All rights reserved.

19. Maternal request for a Caesarean section When a woman requests a Caesarean section because she has anxiety about childbirth, she should be offered referral to a healthcare professional with expertise in providing perinatal mental health support to help her address her anxiety in a supportive manner. For women requesting a Caesarean section, if after dis- cussion and offer of support (including perinatal mental health support for women with anxiety about childbirth), a vaginal birth is still not an acceptable option, planned Caesarean section should be offered. An obstetrician unwilling to perform a Caesarean section should refer the woman to an obstetrician who will carry out the Caesarean section. Pregnancy after 41 weeks’ gestation The final routine visit at 41 weeks’ gestation is designated to discuss and arrange plans for induction of labour if the pregnant woman wishes this. NICE recommends that induction of labour should usually be offered to all women whose pregnancies continue beyond 41 weeks’ gestation. For women who have had a previous Caesarean section, induction of labour, repeat Caesarean section or expectant management should be discussed on an individual basis. Induction during this period is associated with beneficial outcome in terms of reduced Caesarean section rate, reduced operative vaginal delivery, reduced risk of fetal compromise, meconium staining and macrosomia, and reduced risk of fetal and neonatal death. Membrane sweeping in women at term increases the likelihood of both spontaneous labour within 48 hours and birth within 1 week. It is not associated with any increase in adverse maternal or fetal outcomes. As it is a safe procedure and can be performed in the community by the community midwife, it should be offered to all women at term before formal induction of labour. If a woman wishes to avoid induction, increased fetal surveillance should be offered, consisting of at least twice-weekly cardiotocography and ultrasound assessment of liquor volume. It is unclear, however, whether such a policy improves outcomes in these continuing pregnancies. A FURTHER READING Antenatal care: routine care for the healthy pregnant woman. 2008. London: National Collaborating Centre for Women’s and Children’s Health, http://www.nice.org.uk/CG062. Co ˇ te AM, Brown MA, Lam E, et al. Diagnostic accuracy of urinary spot protein:creatinine ratio for proteinuria in hypertensive pregnant women: systematic review. BMJ 2008; http://dx.doi.org/10.1136/ bmj.39532.543947.BE. Diabetes in pregnancy. Management of diabetes and its complications from preconception to the postnatal period. 2015. London: Na- tional Collaborating Centre for Women’s and Children’s Health, http://www.nice.org.uk/NG3. Gardosi J, Francis A. Controlled trial of fundal height measurement plotted on customised antenatal growth charts. Br J Obstet Gynecol 1999; 106: 309e17. Technology appraisal guidance No. 41. Guidance on the use of routine antenatal anti-D prophylaxis for Rh-D negative women. London: NICE, 2002. Hall M, Chang PK, MacGillivray I. Is routine antenatal care worthwhile? Lancet 1980; 2: 78e80. Knight M, Kurinczuk JJ, Spark P, Brocklehurst P. United Kingdom obstetric surveillance system (UKOSS) annual report. Oxford: Na- tional Perinatal Epidemiology Unit, 2007. on behalf of MBRRACE-UK. Saving lives, improving mothers care e surveillance of maternal deaths in the UK 2011e13 and lessons learned to inform maternity care from the UK and Ireland confi- dential enquiries into maternal deaths and morbidity. In: Knight M, Tuffnell D, Kenyon S, Shakespeare J, Gray R, Kurinczak JJ, eds. Oxford: National Perinatal Epidemiology Unit, 2009e2013. Koopmans CM, Bijlenga D, Groen H, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre- eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre open label randomised controlled trial. Lancet 2009; 374: 979e88. Milne F, Redman C, Walker J, et al. The pre-eclampsia community guideline (PRECOG): how to screen for and detect onset of pre- eclampsia in the community. BMJ 2005; 330: 57680. Royal College of Obstetricians and Gynaecologists. Guideline No. 20b. The management of breech presentation. 2006. London: RCOG, http://www.rcog.org.uk/womens-health/clinical-guidance/ management-breech-presentation-green-top-20b. The HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991e2002, http://content.nejm.org/cgi/content/full/358/19/1991. Villar J, Carroli G, Khan-Neelofur D, Piaggio GGP, G€ulmezoglu AM. Patterns of routine antenatal care for low-risk pregnancy. Cochrane Database Syst Rev 2001; http://dx.doi.org/10.1002/14651858. CD000934. Issue 4. Art. No.:CD000934. Weight management before during and after pregnancy. 2010. Lon- don: National Collaborating Centre for Women’s and Children’s Health, http://www.nice.org.uk/PH27. Practice points C The aims of routine antenatal care are the provision of safe and effective care for women with problem-free pregnancies and the detection of common and treatable disorders of pregnancy C Women with problem-free pregnancies should be managed in a community setting to increase satisfaction and reduce intervention C Any deviation from the norm should prompt timely referral to hospital C Care should be based on the evidence suggested; rituals of care unsubstantiated by evidence should be abandoned C Research directions include methods of improving satisfaction whilst achieving low morbidity and mortality with reduced visit schedules C Further studies are required to determine more effective methods for screening for IUGR and its subsequent management once identified C The ACHOIS study suggested careful management of GDM improves outcomes. The HAPO study raises the possibility that milder degrees of maternal hyperglycaemia might also benefit from additional monitoring and/or treatment REVIEW OBSTETRICS, GYNAECOLOGY AND REPRODUCTIVE MEDICINE 26:9 270 Ó 2016 Elsevier Ltd. All rights reserved.

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