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- The death of Sister Evangelina and everyone's reactions, especially Sister Monica Joan's.
- The season four episode with the woman who gives birth to undiagnosed twins, the first of which is stillborn. Not only is the mother's grief gut-wrenching, but the two young midwives attending - Barbara and Patsy - are also devastated but have to put on a brave face and be supportive as best they can. Patsy has to bring the dead baby out to the expectant father and tell him what happened, as well as take charge of the situation since she is more senior than Barbara (who only just began working the previous episode). Phyllis is called to the scene and arrives to find Barbara crying in the kitchen as she's boiling water for the second baby's delivery, and Phyllis' first action is to say "You poor girl" and give Barbara a hug, letting her cry on her shoulder.
- The baby that dies shortly after birth in a season two episode, and the effect it has on Cynthia, the midwife who delivered the baby.
- The death of Alec in season three. Especially since everything seemed to be alright, only for him to develop an embolism and die just an hour after Jenny left his bedside.
- Chummy's distant mother, Lady Browne, is slowly and painfully dying of cancer while at the same time trying to keep her dignity. After trying to help her mother over and over, Chummy finally realizes with help from her friends that the best she can do for her mother is make Lady Browne comfortable at Chummy's home until she passes. She and the others keep watch at her mother's bedside as Chummy does her best to connect with her dying mother and fulfill her requests, even giving her a manicure. As the time draws near, Chummy spills tea on her nursing uniform and is reluctant to change out of it; however, Sister Monica Joan and Jenny tell Chummy it's okay to stop being a nurse and start being a daughter again. Borrowing her mother's robe, Chummy lies down beside Lady Browne and tells her mother she loves her as Lady Browne breathes her last.
- During season five, babies in the neighborhood keep being born with missing limbs and severe birth defects, and no one can figure out why. Dealing with the horrific circumstances are hard enough, particularly in the case of one baby that is born so deformed it dies soon after birth and its gender can't even be determined without autopsy. At last, Dr. Turner receives a notice that Distival note , a medication he had prescribed to several patients to help them with morning sickness, is being withdrawn from the market and may be the cause. He then has the devastating task of going back to the affected families and telling them the drug he gave them that was supposed to help them may have also hurt their babies, or that the children they haven't had yet may be affected by it.
- The season four episode with the baby suffering from brittle bone disease. Not only does it feature a poor infant who gets no less than three broken bones over the course of the episode, he is also taken from his parents because initially they are believed to be the ones responsible (technically they are, but not because of abuse of any kind, but because their baby's bones are so brittle).
- The case where one mother has so taken to Sister Evangelina's insistence that breast milk is best for babies that she resists giving her baby formula even though she has inverted nipples and is not able to nurse properly. Sister Evangelina is so horrified that the mother took her advice so strongly that she leaves temporarily to go to a convent where all the nuns stay silent.
- The episode where Sister Evangelina inadvertently mixes up two babies, giving them to the wrong mother. One then turns out to have a heart murmur and needing a lot of extra care. It's heartbreaking to watch the parents involved, but almost more so to see the normally stoic Sister Evangelina break down to such a degree.
- One episode has a couple arguing over the husband's inability to find work and provide for the family, with his eight months pregnant wife growing increasingly frustrated that he seems to just sit around half the day rather than go out and get work. Eventually she gets so fed-up and worried about how to make ends meet that she throws him out. It then turns out he has leukemia, and only days - weeks at best - to live. Besides dealing with the guilt over having thrown him out, and having to realize and accept that her husband is about to die, she stresses over the birth of her baby. Not out of fear of childbirth, but because she wants her husband to see his child before he dies, and so she asks Barbara to help induce her labor as soon as possible.
- During the course of the fourth season it becomes more and more obvious that Trixie has a drinking problem. After she calls off her engagement to Tom things only get worse. In the last episode of the season she sits alone at night and calls the Samaritans in tears, feeling she has nobody else to turn to. Sister Mary Cynthia overhears, comes over and ends the call (after telling the person on the other end that Trixie is now somewhere safe and not alone), and assures Trixie that she's not alone.
- Everything involving Barbara's death. Septicemia is an awful way to die, and she previously had a Hope Spot that she might survive, although she would have to give up being a midwife due to nerve damage, and then rapidly deteriorated. All of the cast's reaction is devastating, but the worst are her husband, Tom, and Phyllis.