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It is April 1968 and change is coming to Nonnatus House. The sisters intend to make a good impression on new recruit Sister Veronica. It's clear she is no shrinking violet and will ruffle a few feathers. Racial tensions cast a shadow over Poplar following Enoch Powell's incendiary ‘Rivers of Blood' speech. Nancy and Trixie team up to support terminally ill patient, and Fred is saddened to receive an official letter confirming the disbandment of the Civil Defence Corps.

It is May 1968, and the Nonnatus team are faced with challenging cases, one of which is much closer to home as Lucille struggles with her own health. At a coffee morning for expectant mothers, Sister Julienne meets heavily pregnant Lilian Reynolds, who is expecting her first child. However, after Lilian experiences some breast discomfort, she receives a devastating diagnosis.

Meanwhile, Shelagh is organising the Whitsun Maypole celebrations at the eleventh hour. She enlists Cyril, Fred, Dr Turner, Sister Monica Joan, Sister Veronica, Nancy, Violet and Miss Higgins to help, but the preparations for a Maypole dance routine are far from smooth.

It's June 1968, and a carefree Nancy continues to spoil Colette with new gifts. To afford such luxuries Nancy asks Nurse Crane for additional duties, but things come to a head when Nancy is forced to acknowledge her spending is getting out of control.

As health visitor, Sister Veronica visits the Talbot family and is delighted to see them celebrating a joyous occasion. Single mum, Sandy has just married Joe Talbot who treats her children, Peter and Ann Marie, like his own. However, Sister Veronica is shaken when Sandy reveals a terrible truth about her marriage and encourages her to seek help. Meanwhile, kinks remain in Sister Veronica and Nurse Crane's working relationship.

When Nurse Crane attends a ventouse training course at St Cuthbert's, her age is called into question by the consultant running the course, and she is summoned to a meeting with the Board of Health. She starts to question her own abilities and suffers a crisis of confidence whilst overseeing the care of Simone and Larry Lucas who are expecting their second child. They are a young couple living in a council flat, and when the seemingly straightforward delivery runs into problems, Nurse Crane faces the challenges of a traumatic delivery alone.

Meanwhile, Trixie enjoys caring for Vinita Khatri, who is expecting her third child. However, the maternity home is thrown into chaos when an emergency outbreak of gastroenteritis is declared. The team, joined by Sister Monica Joan, must dig deep to ensure all mothers and newborn babies recover from the worrying outbreak. Unfortunately, their actions have not gone unnoticed by the Board of Health, who are less than happy with the way things have been handled.

Reggie is home from the Glasshouse Village, but he is not his usual self. He is drained of energy and suffering some hair loss. Concerned, Violet and Fred try to work out what's wrong, but it is not until Cyril encourages Reggie to seek help that they finally get some answers.

Nancy oversees the care of Jill Mellor and her newborn baby, Mylene, a child she has had out of wedlock with Spencer Wray, a young man from the West Indies. Jill and Spencer live with his kind-hearted mother, Florence. Not long after the birth, Spencer's behaviour starts to raise concerns as it becomes increasingly erratic. Worried, Nancy calls on Dr Turner who refers Spencer for an urgent psychiatric review, but as Spencer's condition deteriorates more rapidly, things take a very unexpected and shocking turn.

Dr Turner and Sister Veronica arrange a men's health talk at the surgery to discuss male contraception and a new procedure, the vasectomy. At the same time, Dr Turner and Nurse Crane care for Annette Berkley, who has rheumatic heart disease and has gone against doctor's advice and fallen pregnant again.

When Matthew's father, Sir Brigham, visits Poplar, relations between father and son are somewhat frosty at best. Matthew's opinion of Poplar is markedly different from his father's, as he has grown fond of the area and its residents over recent years. Matthew wants to invest more money in the borough, whereas Sir Brigham wants to sell up. With relations at an all-time low, Trixie is left to deliver Matthew some heartbreaking news.

Trixie supports an underage mother through a difficult time, Monica Joan welcomes an unusual guest to Nonnatus House, and Sister Veronica spearheads a new council initiative.

It's October 1968, and preparations for Trixie and Matthew's wedding are underway. Nancy makes a home visit to Imelda O'Connor, who is pregnant with her second child, and is surprised that Imelda, her husband Maurice and young son Paul are living in a cramped caravan on a building site. Unbeknown to Nancy, the family's circumstances quickly change when they are made homeless. When their plight is brought to the attention of Nonnatus house, Matthew is very vocal about his views.

Shelagh supports Rosemary Mason, who is expecting her fifth child with husband Arthur. They run a family business selling second-hand goods and also run a guesthouse. Shelagh is troubled by Rosemary's symptoms and consults Dr Turner, who diagnoses Rosemary with hepatitis, a condition that leads to the revelation of a family secret.

Dr Turner soon notices a worrying rise in hepatitis cases throughout the district, and when the outbreak directly impacts the residents of Nonnatus House, the team rally to care for a beloved member. Elsewhere, Cyril returns home from Jamaica and is keen to throw himself into work. He volunteers at a homeless shelter for men and meets a young stricken man, Leon, who is struggling with addiction.

Nonnatus House is abuzz with excitement as the countdown to Trixie and Matthew's wedding begins. Whilst Sister Veronica has appointed herself in charge of organising the wedding gifts, Trixie's brother, Geoffrey Franklin, arrives from Malta and immediately starts arranging the perfect hen do. However, the approaching nuptials cause stress levels to escalate as a catalogue of small and great disasters threaten to spoil the day.

Dr Turner, Shelagh and Timothy are first on the scene of a fatal car crash. Dr Turner experiences the biggest test of his career as they race against time to save a precious life.

Meanwhile, Nancy considers her future, and Sister Julienne hatches a plan to save Nonnatus House once and for all.